Targeting Strategies

  • Ülo LangelEmail author


Biological or therapeutic targeting could be defined as the mechanism(s) by which a biological cargo (drug) is transported to its proper destination, in case of a patient to specific parts of the body, such as diseased tissue.


Targeting Addressing Prodrug Organelles Tissues Plants 


  1. Abbott, N. J., Ronnback, L., & Hansson, E. (2006). Astrocyte-endothelial interactions at the blood-brain barrier. Nature Reviews Neuroscience, 7, 41–53.PubMedCrossRefGoogle Scholar
  2. Acar, H., Ting, J. M., Srivastava, S., Labelle, J. L., & Tirrell, M. V. (2017). Molecular engineering solutions for therapeutic peptide delivery. Chem Soc Rev.Google Scholar
  3. Alexander-Bryant, A. A., Dumitriu, A., Attaway, C. C., Yu, H., & Jakymiw, A. (2015). Fusogenic-oligoarginine peptide-mediated silencing of the CIP2A oncogene suppresses oral cancer tumor growth in vivo. Journal of Control Release, 218, 72–81.CrossRefGoogle Scholar
  4. Alexander-Bryant, A. A., Zhang, H., Attaway, C. C., Pugh, W., Eggart, L., Sansevere, R. M., et al. (2017). Dual peptide-mediated targeted delivery of bioactive siRNAs to oral cancer cells in vivo. Oral Oncology, 72, 123–131.PubMedPubMedCentralCrossRefGoogle Scholar
  5. Alhakamy, N. A., Ishiguro, S., Uppalapati, D., Berkland, C. J., & Tamura, M. (2016). AT2R gene delivered by condensed polylysine complexes attenuates Lewis lung carcinoma after intravenous injection or intratracheal spray. Molecular Cancer Therapeutics, 15, 209–218.PubMedCrossRefGoogle Scholar
  6. Ali, N., Mattsson, K., Rissler, J., Karlsson, H. M., Svensson, C. R., Gudmundsson, A., et al. (2016). Analysis of nanoparticle-protein coronas formed in vitro between nanosized welding particles and nasal lavage proteins. Nanotoxicology, 10, 226–234.PubMedCrossRefGoogle Scholar
  7. Almansour, K., Taverner, A., Turner, J. R., Eggleston, I. M., & Mrsny, R. J. (2018). An intestinal paracellular pathway biased toward positively-charged macromolecules. Journal of Control Release.Google Scholar
  8. Alta, R. Y. P., Vitorino, H. A., Goswami, D., Liria, C. W., Wisnovsky, S. P., Kelley, S. O., et al. (2017). Mitochondria-penetrating peptides conjugated to desferrioxamine as chelators for mitochondrial labile iron. PLoS ONE, 12, e0171729.PubMedPubMedCentralCrossRefGoogle Scholar
  9. Althuon, D., Ronicke, F., Furniss, D., Quan, J., Wellhofer, I., Jung, N., et al. (2015). Functionalized triazolopeptoids—a novel class for mitochondrial targeted delivery. Organic and Biomolecular Chemistry, 13, 4226–4230.PubMedCrossRefGoogle Scholar
  10. Anchordoquy, T. J., Barenholz, Y., Boraschi, D., Chorny, M., Decuzzi, P., Dobrovolskaia, M. A., et al. (2017). Mechanisms and barriers in cancer nanomedicine: Addressing challenges, looking for solutions. ACS Nano, 11, 12–18.PubMedPubMedCentralCrossRefGoogle Scholar
  11. Appelqvist, H., Waster, P., Kagedal, K., & Ollinger, K. (2013). The lysosome: From waste bag to potential therapeutic target. Journal of Molecular Cell Biology, 5, 214–226.PubMedCrossRefGoogle Scholar
  12. Apte, A., Koren, E., Koshkaryev, A., & Torchilin, V. P. (2014). Doxorubicin in TAT peptide-modified multifunctional immunoliposomes demonstrates increased activity against both drug-sensitive and drug-resistant ovarian cancer models. Cancer Biology and Therapy, 15, 69–80.PubMedCrossRefGoogle Scholar
  13. Araujo, F., Shrestha, N., Shahbazi, M. A., Liu, D., Herranz-Blanco, B., Makila, E. M., et al. (2015). Microfluidic assembly of a multifunctional tailorable composite system designed for site specific combined oral delivery of peptide drugs. ACS Nano, 9, 8291–8302.PubMedCrossRefGoogle Scholar
  14. Aronov, O., Horowitz, A. T., Gabizon, A., Fuertes, M. A., Perez, J. M., & Gibson, D. (2004). Nuclear localization signal-targeted poly(ethylene glycol) conjugates as potential carriers and nuclear localizing agents for carboplatin analogues. Bioconjugate Chemistry, 15, 814–823.PubMedCrossRefGoogle Scholar
  15. Arosio, D., & Casagrande, C. (2016). Advancement in integrin facilitated drug delivery. Advanced Drug Delivery Reviews, 97, 111–143.CrossRefGoogle Scholar
  16. Arroyo, J. D., Jourdain, A. A., Calvo, S. E., Ballarano, C. A., Doench, J. G., Root, D. E., et al. (2016). A genome-wide CRISPR death screen identifies genes essential for oxidative phosphorylation. Cell Metabolism, 24, 875–885.PubMedPubMedCentralCrossRefGoogle Scholar
  17. Bae, H. D., Lee, J., Jin, X. H., & Lee, K. (2016). Potential of translationally controlled tumor protein-derived protein transduction domains as antigen carriers for nasal vaccine delivery. Molecular Pharmaceutics, 13, 3196–3205.PubMedPubMedCentralCrossRefGoogle Scholar
  18. Bae, H. D., Lee, J., Jun, K. Y., Kwon, Y., & Lee, K. (2018). Modification of translationally controlled tumor protein-derived protein transduction domain for improved intranasal delivery of insulin. Drug Delivery, 25, 1025–1032.PubMedPubMedCentralCrossRefGoogle Scholar
  19. Baker, R. D., Howl, J., & Nicholl, I. D. (2007). A sychnological cell penetrating peptide mimic of p21(WAF1/CIP1) is pro-apoptogenic. Peptides, 28, 731–740.PubMedPubMedCentralCrossRefGoogle Scholar
  20. Banks, W. A. (2015). Peptides and the blood-brain barrier. Peptides, 72, 16–19.PubMedPubMedCentralCrossRefGoogle Scholar
  21. Banks, W. A., Kastin, A. J., Huang, W., Jaspan, J. B., & Maness, L. M. (1996). Leptin enters the brain by a saturable system independent of insulin. Peptides, 17, 305–311.PubMedCrossRefGoogle Scholar
  22. Barbari, G. R., Dorkoosh, F., Amini, M., Bahari Javan, N., Sharifzadeh, M., Atyabi, F., et al. (2018). Synthesis and characterization of a novel peptide-grafted Cs and evaluation of its nanoparticles for the oral delivery of insulin, in vitro, and in vivo study. International Journal of Nanomedicine, 13, 5127–5138.CrossRefGoogle Scholar
  23. Barnes, W. J., & Anderson, C. T. (2017). Release, recycle, rebuild: Cell wall remodeling, autodegradation, and sugar salvage for new wall biosynthesis during plant development. Molecular Plant.Google Scholar
  24. Batista da Cunha, D., Pupo Silvestrini, A. V., Gomes da Silva, A. C., Maria de Paula Estevam, D., Pollettini, F. L., De Oliveira Navarro, J., et al. (2018). Mechanistic insights into functional characteristics of native crotamine. Toxicon, 146, 1–12.PubMedCrossRefGoogle Scholar
  25. Begley, D. J., & Brightman, M. W. (2003). Structural and functional aspects of the blood-brain barrier. Progress in Drug Research, 61, 39–78.PubMedGoogle Scholar
  26. Ben Djemaa, S., David, S., Herve-Aubert, K., Falanga, A., Galdiero, S., Allard-Vannier, E., et al. (2018). Formulation and in vitro evaluation of a siRNA delivery nanosystem decorated with gH625 peptide for triple negative breast cancer theranosis. European Journal of Pharmaceutics and Biopharmaceutics.Google Scholar
  27. Berry, C. C., de la Fuente, J. M., Mullin, M., Chu, S. W., & Curtis, A. S. (2007). Nuclear localization of HIV-1 tat functionalized gold nanoparticles. IEEE Transactions on Nanobioscience, 6, 262–269.PubMedCrossRefGoogle Scholar
  28. Bertrand, N., & Leroux, J.-C. (2012). The journey of a drug-carrier in the body: An anatomo-physiological perspective. Journal of Controlled Release, 161, 152–163.PubMedCrossRefGoogle Scholar
  29. Bhunia, D., Mondal, P., Das, G., Saha, A., Sengupta, P., Jana, J., et al. (2018). Spatial position regulates power of tryptophan: Discovery of a major-groove-specific nuclear-localizing, cell-penetrating tetrapeptide. Journal of the American Chemical Society.Google Scholar
  30. Bhutia, S. K., Mallick, S. K., Maiti, S., Mishra, D., & Maiti, T. K. (2009). Abrus abrin derived peptides induce apoptosis by targeting mitochondria in HeLa cells. Cell Biology International, 33, 720–727.PubMedCrossRefGoogle Scholar
  31. Bidwell, G. L., III, Davis, A. N., & Raucher, D. (2009). Targeting a c-Myc inhibitory polypeptide to specific intracellular compartments using cell penetrating peptides. Journal of Controlled Release, 135, 2–10.PubMedCrossRefGoogle Scholar
  32. Bilichak, A., Luu, J., & Eudes, F. (2015). Intracellular delivery of fluorescent protein into viable wheat microspores using cationic peptides. Frontiers in Plant Science, 6.Google Scholar
  33. Biswas, S., Deshpande, P. P., Perche, F., Dodwadkar, N. S., Sane, S. D., & Torchilin, V. P. (2013). Octa-arginine-modified pegylated liposomal doxorubicin: An effective treatment strategy for non-small cell lung cancer. Cancer Letters, 335, 191–200.PubMedPubMedCentralCrossRefGoogle Scholar
  34. Bolhassani, A. (2011). Potential efficacy of cell-penetrating peptides for nucleic acid and drug delivery in cancer. Biochimica et Biophysica Acta, 1816, 232–246.PubMedGoogle Scholar
  35. Bolhassani, A., Jafarzade, B. S., & Mardani, G. (2017). In vitro and in vivo delivery of therapeutic proteins using cell penetrating peptides. Peptides, 87, 50–63.CrossRefGoogle Scholar
  36. Bonifacino, J. S., & Dell’Angelica, E. C. (1999). Molecular bases for the recognition of tyrosine-based sorting signals. Journal of Cell Biology, 145, 923–926.PubMedCrossRefGoogle Scholar
  37. Bowerman, C. J., & Nilsson, B. L. (2010). A reductive trigger for peptide self-assembly and hydrogelation. Journal of the American Chemical Society, 132, 9526–9527.PubMedCrossRefGoogle Scholar
  38. Brasnjevic, I., Steinbusch, H. W., Schmitz, C., & Martinez-Martinez, P. (2009). Delivery of peptide and protein drugs over the blood-brain barrier. Progress in Neurobiology, 87, 212–251.PubMedCrossRefGoogle Scholar
  39. Brayden, D. J., & Mrsny, R. J. (2011). Oral peptide delivery: Prioritizing the leading technologies. Therapeutic Delivery, 2, 1567–1573.PubMedCrossRefGoogle Scholar
  40. Brunner, J., & Barton, J. K. (2006). Targeting DNA mismatches with rhodium intercalators functionalized with a cell-penetrating peptide. Biochemistry, 45, 12295–12302.PubMedCrossRefGoogle Scholar
  41. Buckley, S. T., Hubalek, F., & Rahbek, U. L. (2016). Chemically modified peptides and proteins—Critical considerations for oral delivery. Tissue Barriers, 4, Apr–Jun.Google Scholar
  42. Cantini, L., Attaway, C. C., Butler, B., Andino, L. M., Sokolosky, M. L., & Jakymiw, A. (2013). Fusogenic-oligoarginine peptide-mediated delivery of siRNAs targeting the CIP2A oncogene into oral cancer cells. PLoS ONE, 8, e73348.PubMedPubMedCentralCrossRefGoogle Scholar
  43. Cardo, L., Thomas, S. G., Mazharian, A., Pikramenou, Z., Rappoport, J. Z., Hannon, M. J., et al. (2015). Accessible synthetic probes for staining actin inside platelets and megakaryocytes by employing lifeact peptide. ChemBioChem, 16, 1680–1688.PubMedPubMedCentralCrossRefGoogle Scholar
  44. Carmichael, N. M., Dostrovsky, J. O., & Charlton, M. P. (2010). Peptide-mediated transdermal delivery of botulinum neurotoxin type A reduces neurogenic inflammation in the skin. Pain, 149, 316–324.PubMedCrossRefGoogle Scholar
  45. Cerrato, C. P., Künnapuu, K., & Langel, Ü. (2017). Cell-penetrating peptides with intracellular organelle targeting. Expert Opinion on Drug Delivery, 14, 245–255.PubMedCrossRefGoogle Scholar
  46. Cerrato, C. P., & Langel, U. (2017). Effect of a fusion peptide by covalent conjugation of a mitochondrial cell-penetrating peptide and a glutathione analog peptide. Molecular Therapy-Methods and Clinical Development, 5, 221–231.PubMedCrossRefGoogle Scholar
  47. Cerrato, C. P., Pirisinu, M., Vlachos, E. N., & Langel, Ü. (2015). Novel cell-penetrating peptide targeting mitochondria. FASEB Journal, 29, 4589–4599.CrossRefGoogle Scholar
  48. Chang, M., Chou, J.-C., & Lee, H.-J. (2005). Cellular internalization of fluorescent proteins via arginine-rich intracellular delivery peptide in plant cells. Plant and Cell Physiology, 46, 482–488.PubMedCrossRefGoogle Scholar
  49. Chang, M., Chou, J. C., Chen, C. P., Liu, B. R., & Lee, H. J. (2007). Noncovalent protein transduction in plant cells by macropinocytosis. New Phytologist, 174, 46–56.PubMedCrossRefGoogle Scholar
  50. Chen, B., Friedman, B., Whitney, M. A., Winkle, J. A., Lei, I. F., Olson, E. S., et al. (2012). Thrombin activity associated with neuronal damage during acute focal ischemia. Journal of Neuroscience, 32, 7622–7631.PubMedCrossRefGoogle Scholar
  51. Chen, C.-P., Chou, J.-C., Liu, B. R., Chang, M., & Lee, H.-J. (2007). Transfection and expression of plasmid DNA in plant cells by an arginine-rich intracellular delivery peptide without protoplast preparation. FEBS Letters, 581, 1891–1897.PubMedCrossRefGoogle Scholar
  52. Chen, H. C., Chiou, S. T., Zheng, J. Y., Yang, S. H., Lai, S. S., & Kuo, T. Y. (2011). The nuclear localization signal sequence of porcine circovirus type 2 ORF2 enhances intracellular delivery of plasmid DNA. Archives of Virology, 156, 803–815.PubMedCrossRefGoogle Scholar
  53. Chen, M., Kumar, S., Anselmo, A. C., Gupta, V., Slee, D. H., Muraski, J. A., et al. (2015). Topical delivery of Cyclosporine A into the skin using SPACE-peptide. Journal of Control Release, 199, 190–197.CrossRefGoogle Scholar
  54. Chen, M., Zakrewsky, M., Gupta, V., Anselmo, A. C., Slee, D. H., Muraski, J. A., et al. (2014a). Topical delivery of siRNA into skin using SPACE-peptide carriers. Journal of Control Release, 179, 33–41.CrossRefGoogle Scholar
  55. Chen, Q., & Lai, H. (2015). Gene delivery into plant cells for recombinant protein production. BioMed Research International, 2015, 932161.PubMedPubMedCentralGoogle Scholar
  56. Chen, Q., Lai, H., Hurtado, J., Stahnke, J., Leuzinger, K., & Dent, M. (2013). Agroinfiltration as an effective and scalable strategy of gene delivery for production of pharmaceutical proteins. Advanced Techniques in Biology & Medicine, 1.Google Scholar
  57. Chen, Y., & Liu, L. (2012). Modern methods for delivery of drugs across the blood-brain barrier. Advanced Drug Delivery Reviews, 64, 640–665.PubMedCrossRefGoogle Scholar
  58. Chen, Y., Shen, Y., Guo, X., Zhang, C., Yang, W., Ma, M., et al. (2006). Transdermal protein delivery by a coadministered peptide identified via phage display. Nature Biotechnology, 24, 455–460.PubMedPubMedCentralCrossRefGoogle Scholar
  59. Chen, Z., Zhang, P., Cheetham, A. G., Moon, J. H., Moxley, J. W., Jr., Lin, Y. A. et al. (2014b). Controlled release of free doxorubicin from peptide-drug conjugates by drug loading. Journal of Control Release, 191, 123–130.PubMedCrossRefGoogle Scholar
  60. Cheng, H., Zhu, J. Y., Xu, X. D., Qiu, W. X., Lei, Q., Han, K., et al. (2015). Activable cell-penetrating peptide conjugated prodrug for tumor targeted drug delivery. ACS Applied Materials and Interfaces, 7, 16061–16069.PubMedCrossRefGoogle Scholar
  61. Cheng, Y., Huang, F., Min, X., Gao, P., Zhang, T., Li, X., et al. (2016). Protease-responsive prodrug with aggregation-induced emission probe for controlled drug delivery and drug release tracking in living cells. Analytical Chemistry, 88, 8913–8919.PubMedCrossRefGoogle Scholar
  62. Choi, D. K., Bae, J., Shin, S. M., Shin, J. Y., Kim, S., & Kim, Y. S. (2014). A general strategy for generating intact, full-length IgG antibodies that penetrate into the cytosol of living cells. MAbs, 6, 1402–1414.PubMedPubMedCentralCrossRefGoogle Scholar
  63. Choi, S. W., Pangeni, R., Jung, D. H., Kim, S. J., & Park, J. W. (2018). Construction and characterization of cell-penetrating peptide-fused fibroblast growth factor and vascular endothelial growth factor for an enhanced percutaneous delivery system. Journal of Nanoscience and Nanotechnology, 18, 842–847.PubMedCrossRefGoogle Scholar
  64. Choi, Y., Kim, K., Hong, S., Kim, H., Kwon, Y. J., & Song, R. (2011). Intracellular protein target detection by quantum dots optimized for live cell imaging. Bioconjugate Chemistry, 22, 1576–1586.PubMedCrossRefGoogle Scholar
  65. Chuah, J. A., Horii, Y., & Numata, K. (2016a). Peptide-derived method to transport genes and proteins across cellular and organellar barriers in plants. Journal of Visualized Experiments.Google Scholar
  66. Chuah, J. A., Matsugami, A., Hayashi, F., & Numata, K. (2016b). Self-assembled peptide-based system for mitochondrial-targeted gene delivery: Functional and structural insights. Biomacromolecules, 17, 3547–3557.PubMedPubMedCentralCrossRefGoogle Scholar
  67. Chuah, J. A., & Numata, K. (2018). Stimulus-responsive peptide for effective delivery and release of DNA in plants. Biomacromolecules.Google Scholar
  68. Chuah, J. A., Yoshizumi, T., Kodama, Y., & Numata, K. (2015). Gene introduction into the mitochondria of Arabidopsis thaliana via peptide-based carriers. Scientific Reports, 5, 7751.PubMedPubMedCentralCrossRefGoogle Scholar
  69. Chuard, N., Fujisawa, K., Morelli, P., Saarbach, J., Winssinger, N., Metrangolo, P., et al. (2016). Activation of cell-penetrating peptides with Ionpair-pi interactions and fluorophiles. Journal of the American Chemical Society, 138, 11264–11271.PubMedPubMedCentralCrossRefGoogle Scholar
  70. Chugh, A., Amundsen, E., & Eudes, F. (2009). Translocation of cell-penetrating peptides and delivery of their cargoes in triticale microspores. Plant Cell Reports, 28, 801–810.PubMedCrossRefGoogle Scholar
  71. Chugh, A., & Eudes, F. (2007). Translocation and nuclear accumulation of monomer and dimer of HIV-1 Tat basic domain in triticale mesophyll protoplasts. Biochimica et Biophysica Acta, 1768, 419–426.PubMedCrossRefGoogle Scholar
  72. Chugh, A., & Eudes, F. (2008a). Cellular uptake of cell-penetrating peptides pVEC and transportan in plants. Journal of Peptide Science, 14, 477–481.CrossRefGoogle Scholar
  73. Chugh, A., & Eudes, F. (2008b). Study of uptake of cell penetrating peptides and their cargoes in permeabilized wheat immature embryos. FEBS Journal, 275, 2403–2414.PubMedCrossRefGoogle Scholar
  74. Cohen-Avrahami, M., Shames, A. I., Ottaviani, M. F., Aserin, A., & Garti, N. (2014). HIV-TAT enhances the transdermal delivery of NSAID drugs from liquid crystalline mesophases. The Journal of Physical Chemistry B, 118, 6277–6287.PubMedPubMedCentralCrossRefGoogle Scholar
  75. Collard, R., Majtan, T., Park, I., & Kraus, J. P. (2018). Import of TAT-conjugated propionyl-CoA carboxylase using models of propionic acidemia. Molecular and Cellular Biology.Google Scholar
  76. Collombet, J.-M., Wheeler, V. C., Vogel, F., & Coutelle, C. (1997). Introduction of plasmid DNA into isolated mitochondria by electroporation: A novel approach toward gene correction for mitochondrial disorders. Journal of Biological Chemistry, 272, 5342–5347.PubMedCrossRefGoogle Scholar
  77. Colombo, M., Mizzotti, C., Masiero, S., Kater, M. M., & Pesaresi, P. (2015). Peptide aptamers: The versatile role of specific protein function inhibitors in plant biotechnology. Journal of Integrative Plant Biology, 57, 892–901.PubMedPubMedCentralCrossRefGoogle Scholar
  78. Craven, L., Alston, C. L., Taylor, R. W., & Turnbull, D. M. (2017). Recent advances in mitochondrial disease. Annual Review of Genomics and Human Genetics, 17, 091416-035426.Google Scholar
  79. Crisp, J. L., Savariar, E. N., Glasgow, H. L., Ellies, L. G., Whitney, M. A., & Tsien, R. Y. (2014). Dual targeting of integrin alphavbeta3 and matrix metalloproteinase-2 for optical imaging of tumors and chemotherapeutic delivery. Molecular Cancer Therapeutics, 13, 1514–1525.PubMedPubMedCentralCrossRefGoogle Scholar
  80. Danielsen, E. M., & Hansen, G. H. (2018). Impact of cell-penetrating peptides (CPPs) melittin and Hiv-1 Tat on the enterocyte brush border using a mucosal explant system. Biochimica et Biophysica Acta, 1860, 1589–1599.PubMedCrossRefGoogle Scholar
  81. de Boer, A. G., & Gaillard, P. J. (2007). Strategies to improve drug delivery across the blood-brain barrier. Clinical Pharmacokinetics, 46, 553–576.PubMedCrossRefGoogle Scholar
  82. de Boer, A. G., van der Sandt, I. C., & Gaillard, P. J. (2003). The role of drug transporters at the blood-brain barrier. Annual Review of Pharmacology and Toxicology, 43, 629–656.PubMedCrossRefGoogle Scholar
  83. de Kruijf, W., & Ehrhardt, C. (2017). Inhalation delivery of complex drugs-the next steps. Current Opinion in Pharmacology, 36, 52–57.PubMedCrossRefGoogle Scholar
  84. Deb, R., & Nagotu, S. (2017). Versatility of peroxisomes: An evolving concept. Tissue and Cell, 49, 209–226.PubMedCrossRefGoogle Scholar
  85. Dekiwadia, C. D., Lawrie, A. C., & Fecondo, J. V. (2012). Peptide-mediated cell penetration and targeted delivery of gold nanoparticles into lysosomes. Journal of Peptide Science, 18, 527–534.PubMedCrossRefGoogle Scholar
  86. Demeule, M., Poirier, J., Jodoin, J., Bertrand, Y., Desrosiers, R. R., Dagenais, C., et al. (2002). High transcytosis of melanotransferrin (P97) across the blood-brain barrier. Journal of Neurochemistry, 83, 924–933.PubMedCrossRefGoogle Scholar
  87. Demeule, M., Regina, A., Che, C., Poirier, J., Nguyen, T., Gabathuler, R., et al. (2008). Identification and design of peptides as a new drug delivery system for the brain. Journal of Pharmacology and Experimental Therapeutics, 324, 1064–1072.PubMedCrossRefGoogle Scholar
  88. Desai, P. R., Cormier, A. R., Shah, P. P., Patlolla, R. R., Paravastu, A. K., & Singh, M. (2014). (31)P solid-state NMR based monitoring of permeation of cell penetrating peptides into skin. European Journal of Pharmaceutics and Biopharmaceutics, 86, 190–199.PubMedPubMedCentralCrossRefGoogle Scholar
  89. Dietz, G. P., Valbuena, P. C., Dietz, B., Meuer, K., Mueller, P., Weishaupt, J. H., et al. (2006). Application of a blood-brain-barrier-penetrating form of GDNF in a mouse model for Parkinson’s disease. Brain Research, 1082, 61–66.PubMedCrossRefGoogle Scholar
  90. Ding, Q., Markesbery, W. R., Chen, Q., Li, F., & Keller, J. N. (2005). Ribosome dysfunction is an early event in Alzheimer’s disease. Journal of Neuroscience, 25, 9171–9175.PubMedCrossRefGoogle Scholar
  91. Doeppner, T. R., Nagel, F., Dietz, G. P., Weise, J., Tonges, L., Schwarting, S., et al. (2009). TAT-Hsp70-mediated neuroprotection and increased survival of neuronal precursor cells after focal cerebral ischemia in mice. Journal of Cerebral Blood Flow and Metabolism, 29, 1187–1196.CrossRefGoogle Scholar
  92. Dominska, M., & Dykxhoorn, D. M. (2010). Breaking down the barriers: siRNA delivery and endosome escape. Journal of Cell Science, 123, 1183–1189.PubMedCrossRefGoogle Scholar
  93. Dondi, R., Yaghini, E., Tewari, K. M., Wang, L., Giuntini, F., Loizidou, M., et al. (2016). Flexible synthesis of cationic peptide-porphyrin derivatives for light-triggered drug delivery and photodynamic therapy. Organic and Biomolecular Chemistry, 14, 11488–11501.PubMedCrossRefGoogle Scholar
  94. Doran, P. M. (2013). Therapeutically important proteins from in vitro plant tissue culture systems. Current Medicinal Chemistry, 20, 1047–1055.PubMedGoogle Scholar
  95. Drin, G., Cottin, S., Blanc, E., Rees, A. R., & Temsamani, J. (2003). Studies on the internalization mechanism of cationic cell-penetrating peptides. Journal of Biological Chemistry, 278, 31192–31201.PubMedPubMedCentralCrossRefGoogle Scholar
  96. Drin, G., Rousselle, C., Scherrmann, J. M., Rees, A. R. & Temsamani, J. (2002). Peptide delivery to the brain via adsorptive-mediated endocytosis: Advances with SynB vectors. AAPS PharmSci, 4.Google Scholar
  97. Dube, T., Chibh, S., Mishra, J. & Panda, J. J. (2017). Receptor targeted polymeric nanostructures capable of navigating across the blood-brain barrier for effective delivery of neural therapeutics. ACS Chemical Neuroscience, 25.Google Scholar
  98. Eggenberger, K., Birtalan, E., Schroder, T., Brase, S., & Nick, P. (2009). Passage of Trojan peptoids into plant cells. ChemBioChem, 10, 2504–2512.PubMedCrossRefGoogle Scholar
  99. Eriste, E., Kurrikoff, K., Suhorutsenko, J., Oskolkov, N., Copolovici, D. M., Jones, S., et al. (2013). Peptide-based glioma-targeted drug delivery vector gHoPe2. Bioconjugate Chemistry, 24, 305–313.PubMedPubMedCentralCrossRefGoogle Scholar
  100. Erlich-Hadad, T., Hadad, R., Feldman, A., Greif, H., Lictenstein, M., & Lorberboum-Galski, H. (2018). TAT-MTS-MCM fusion proteins reduce MMA levels and improve mitochondrial activity and liver function in MCM-deficient cells. Journal of Cellular and Molecular Medicine, 22, 1601–1613.PubMedCrossRefGoogle Scholar
  101. Eudes, F., & Macmillan, T. (2014). Organelle targeting nanocarriers. Google Patents.Google Scholar
  102. Feng, X., Gao, X., Kang, T., Jiang, D., Yao, J., Jing, Y., et al. (2015). Mammary-derived growth inhibitor targeting peptide-modified PEG-PLA nanoparticles for enhanced targeted glioblastoma therapy. Bioconjugate Chemistry, 26, 1850–1861.PubMedCrossRefGoogle Scholar
  103. Fillebeen, C., Descamps, L., Dehouck, M. P., Fenart, L., Benaissa, M., Spik, G., et al. (1999). Receptor-mediated transcytosis of lactoferrin through the blood-brain barrier. Journal of Biological Chemistry, 274, 7011–7017.PubMedCrossRefGoogle Scholar
  104. Fischer, R., Bachle, D., Fotin-Mleczek, M., Jung, G., Kalbacher, H., & Brock, R. (2006). A targeted protease substrate for a quantitative determination of protease activities in the endolysosomal pathway. ChemBioChem, 7, 1428–1434.PubMedCrossRefGoogle Scholar
  105. Fischer, R., Kohler, K., Fotin-Mleczek, M., & Brock, R. (2004). A stepwise dissection of the intracellular fate of cationic cell-penetrating peptides. Journal of Biological Chemistry, 279, 12625–12635.PubMedPubMedCentralCrossRefGoogle Scholar
  106. Fisher, L., Samuelsson, M., Jiang, Y., Ramberg, V., Figueroa, R., Hallberg, E., et al. (2007). Targeting cytokine expression in glial cells by cellular delivery of an NF-kappaB decoy. Journal of Molecular Neuroscience, 31, 209–219.Google Scholar
  107. Foger, F., Kopf, A., Loretz, B., Albrecht, K., & Bernkop-Schnurch, A. (2008). Correlation of in vitro and in vivo models for the oral absorption of peptide drugs. Amino Acids, 35, 233–241.PubMedCrossRefGoogle Scholar
  108. Fonseca, S. B., Pereira, M. P., Mourtada, R., Gronda, M., Horton, K. L., Hurren, R., et al. (2011). Rerouting chlorambucil to mitochondria combats drug deactivation and resistance in cancer cells. Chemistry and Biology, 18, 445–453.PubMedCrossRefGoogle Scholar
  109. Fortin, D., Gendron, C., Boudrias, M., & Garant, M. P. (2007). Enhanced chemotherapy delivery by intraarterial infusion and blood-brain barrier disruption in the treatment of cerebral metastasis. Cancer, 109, 751–760.PubMedCrossRefGoogle Scholar
  110. Frankenburg, S., Grinberg, I., Bazak, Z., Fingerut, L., Pitcovski, J., Gorodetsky, R., et al. (2007). Immunological activation following transcutaneous delivery of HR-gp100 protein. Vaccine, 25, 4564–4570.PubMedPubMedCentralCrossRefGoogle Scholar
  111. Fretz, M. M., Penning, N. A., Al-Taei, S., Futaki, S., Takeuchi, T., Nakase, I., et al. (2007). Temperature-, concentration- and cholesterol-dependent translocation of L- and D-octa-arginine across the plasma and nuclear membrane of CD34+ leukaemia cells. Biochemical Journal, 403, 335–342.PubMedPubMedCentralCrossRefGoogle Scholar
  112. Friden, P. M., Walus, L. R., Musso, G. F., Taylor, M. A., Malfroy, B., & Starzyk, R. M. (1991). Anti-transferrin receptor antibody and antibody-drug conjugates cross the blood-brain barrier. Proceedings of the National Academy of Sciences, 88, 4771–4775.CrossRefGoogle Scholar
  113. Fu, A., Wang, Y., Zhan, L., & Zhou, R. (2012). Targeted delivery of proteins into the central nervous system mediated by rabies virus glycoprotein-derived peptide. Pharmaceutical Research, 29, 1562–1569.PubMedCrossRefGoogle Scholar
  114. Fukuoka, Y., Khafagy, E. S., Goto, T., Kamei, N., Takayama, K., Peppas, N. A., et al. (2018). Combination strategy with complexation hydrogels and cell-penetrating peptides for oral delivery of insulin. Biological &/and Pharmaceutical Bulletin, 41, 811–814.CrossRefGoogle Scholar
  115. Furukawa, R., Yamada, Y., Kawamura, E., & Harashima, H. (2015). Mitochondrial delivery of antisense RNA by MITO-Porter results in mitochondrial RNA knockdown, and has a functional impact on mitochondria. Biomaterials, 57, 107–115.PubMedCrossRefGoogle Scholar
  116. Gaillard, P. J., Visser, C. C., & de Boer, A. G. (2005). Targeted delivery across the blood-brain barrier. Expert Opinion on Drug Delivery, 2, 299–309.PubMedCrossRefGoogle Scholar
  117. Gaizo, V. D., Mackenzie, J. A., & Payne, R. M. (2003). Targeting proteins to mitochondria using TAT. Molecular Genetics and Metabolism, 80, 170–180.PubMedCrossRefGoogle Scholar
  118. Gan, H. K., van den Bent, M., Lassman, A. B., Reardon, D. A., & Scott, A. M. (2017). Antibody-drug conjugates in glioblastoma therapy: The right drugs to the right cells. Nature Reviews Clinical Oncology, 4, 95.Google Scholar
  119. Gao, C., Hong, M., Geng, J., Zhou, H., & Dong, J. (2015). Characterization of PI (breast cancer cell special peptide) in MDA-MB-231 breast cancer cells and its potential therapeutic applications. International Journal of Oncology, 47, 1371–1378.PubMedCrossRefGoogle Scholar
  120. Gao, H., Zhang, S., Cao, S., Yang, Z., Pang, Z., & Jiang, X. (2014). Angiopep-2 and activatable cell-penetrating peptide dual-functionalized nanoparticles for systemic glioma-targeting delivery. Molecular Pharmaceutics, 11, 2755–2763.PubMedCrossRefGoogle Scholar
  121. Gao, J., Wang, L., Liu, J., Xie, F., Su, B., & Wang, X. (2017). Abnormalities of mitochondrial dynamics in neurodegenerative diseases. Antioxidants, 6.Google Scholar
  122. Gao, W., Xiang, B., Meng, T. T., Liu, F., & Qi, X. R. (2013). Chemotherapeutic drug delivery to cancer cells using a combination of folate targeting and tumor microenvironment-sensitive polypeptides. Biomaterials, 34, 4137–4149.PubMedCrossRefGoogle Scholar
  123. Garcia-Lopez, V., Chen, F., Nilewski, L. G., Duret, G., Aliyan, A., Kolomeisky, A. B., et al. (2017). Molecular machines open cell membranes. Nature, 548, 567–572.PubMedCrossRefGoogle Scholar
  124. Garcia, J., Fernandez-Blanco, A., Teixido, M., Sanchez-Navarro, M., & Giralt, E. (2018). d-Polyarginine lipopeptides as intestinal permeation enhancers. ChemMedChem.Google Scholar
  125. Gautam, A., Nanda, J. S., Samuel, J. S., Kumari, M., Priyanka, P., Bedi, G., et al. (2016). Topical delivery of protein and peptide using novel cell penetrating peptide IMT-P8. Scientific Reports, 6.Google Scholar
  126. Gehrmann, M., Stangl, S., Foulds, G. A., Oellinger, R., Breuninger, S., Rad, R., et al. (2014). Tumor imaging and targeting potential of an Hsp70-derived 14-mer peptide. PLoS ONE, 9, e105344.PubMedPubMedCentralCrossRefGoogle Scholar
  127. Geisler, I. M., & Chmielewski, J. (2011). Dimeric cationic amphiphilic polyproline helices for mitochondrial targeting. Pharmaceutical Research, 28, 2797–2807.PubMedCrossRefGoogle Scholar
  128. Gennari, C. G., Franze, S., Pellegrino, S., Corsini, E., Vistoli, G., Montanari, L., et al. (2016). Skin penetrating peptide as a tool to enhance the permeation of heparin through human epidermis. Biomacromolecules, 17, 46–55.PubMedPubMedCentralCrossRefGoogle Scholar
  129. Gerard, G. M. D. S., & Volkmar, W. (2004). Approaches to mitochondrial gene therapy. Current Gene Therapy, 4, 317–328.CrossRefGoogle Scholar
  130. Golestanipour, A., Nikkhah, M., Aalami, A., & Hosseinkhani, S. (2018). Gene delivery to tobacco root cells with single-walled carbon nanotubes and cell-penetrating fusogenic peptides. Molecular Biotechnology.Google Scholar
  131. Gonias, S. L., & Campana, W. M. (2014). LDL receptor-related protein-1: A regulator of inflammation in atherosclerosis, cancer, and injury to the nervous system. American Journal of Pathology, 184, 18–27.PubMedCrossRefGoogle Scholar
  132. Gopalakrishnan, S., Pandey, N., Tamiz, A. P., Vere, J., Carrasco, R., Somerville, R., et al. (2009). Mechanism of action of ZOT-derived peptide AT-1002, a tight junction regulator and absorption enhancer. International Journal of Pharmaceutics, 365, 121–130.PubMedPubMedCentralCrossRefGoogle Scholar
  133. Gorman, G. S., Chinnery, P. F., Dimauro, S., Hirano, M., Koga, Y., Mcfarland, R., et al. (2016). Nature Reviews Disease Primers, 2:16080 10.1038/nrdp.2016.80.
  134. Gotanda, Y., Wei, F. Y., Harada, H., Ohta, K., Nakamura, K., Tomizawa, K., et al. (2014). Efficient transduction of 11 poly-arginine peptide in an ischemic lesion of mouse brain. Journal of Stroke and Cerebrovascular Diseases, 23, 2023–2030.PubMedCrossRefGoogle Scholar
  135. Goun, E. A., Shinde, R., Dehnert, K. W., Adams-Bond, A., Wender, P. A., Contag, C. H., et al. (2006). Intracellular cargo delivery by an octaarginine transporter adapted to target prostate cancer cells through cell surface protease activation. Bioconjugate Chemistry, 17, 787–796.PubMedCrossRefGoogle Scholar
  136. Govindarajan, S., Sivakumar, J., Garimidi, P., Rangaraj, N., Kumar, J. M., Rao, N. M., et al. (2012). Targeting human epidermal growth factor receptor 2 by a cell-penetrating peptide-affibody bioconjugate. Biomaterials, 33, 2570–2582.PubMedPubMedCentralCrossRefGoogle Scholar
  137. Griffin, J. I., Cheng, S. K. K., Hayashi, T., Carson, D., Saraswathy, M., Nair, D. P., et al. (2017). Cell-penetrating peptide CGKRK mediates efficient and widespread targeting of bladder mucosa following focal injury. Nanomedicine (Lond), 13, 1925–1932.CrossRefGoogle Scholar
  138. Gronewold, A., Horn, M., & Neundorf, I. (2018). Design and biological characterization of novel cell-penetrating peptides preferentially targeting cell nuclei and subnuclear regions. Beilstein Journal of Organic Chemistry, 14, 1378–1388.PubMedPubMedCentralCrossRefGoogle Scholar
  139. Gross, A., Alborzinia, H., Piantavigna, S., Martin, L. L., Wolfl, S., & Metzler-Nolte, N. (2015). Vesicular disruption of lysosomal targeting organometallic polyarginine bioconjugates. Metallomics, 7, 371–384.PubMedCrossRefGoogle Scholar
  140. Gul, R., Ahmed, N., Shah, K. U., Khan, G. M., & Ur Rehman, A. (2017). Functionalized nanostructures for transdermal delivery of drug cargos. Journal of Drug Targeting, 31, 1–30.Google Scholar
  141. Gupta, S., Jain, A., Chakraborty, M., Sahni, J. K., Ali, J., & Dang, S. (2013). Oral delivery of therapeutic proteins and peptides: A review on recent developments. Drug Delivery, 20, 237–246.PubMedCrossRefGoogle Scholar
  142. Gupta, U., Kumar, H., Mishra, G., Kumar Sharma, A., Gothwal, A. & Kesharwani, P. (2017). Intranasal drug delivery: A non-invasive approach for the better delivery of neurotherapeutics. Pharmaceutical Nanotechnology, 14, 2211738505666170515113936.Google Scholar
  143. Haeckel, A., Appler, F., Ariza de Schellenberger, A., & Schellenberger, E. (2016). XTEN as biological alternative to PEGylation allows complete expression of a protease-activatable killin-based cytostatic. PLoS One, 11.Google Scholar
  144. Han, S. S., Li, Z. Y., Zhu, J. Y., Han, K., Zeng, Z. Y., Hong, W., et al. (2015). Dual-pH sensitive charge-reversal polypeptide micelles for tumor-triggered targeting uptake and nuclear drug delivery. Small (Weinheim an der Bergstrasse, Germany), 11, 2543–2554.CrossRefGoogle Scholar
  145. Hansen, A., Schafer, I., Knappe, D., Seibel, P., & Hoffmann, R. (2012). Intracellular toxicity of proline-rich antimicrobial peptides shuttled into mammalian cells by the cell-penetrating peptide penetratin. Antimicrobial Agents and Chemotherapy, 56, 5194–5201.PubMedPubMedCentralCrossRefGoogle Scholar
  146. Hansen, M., Kilk, K., & Langel, Ü. (2008). Predicting cell-penetrating peptides. Advanced Drug Delivery Reviews, 60, 572–579.PubMedPubMedCentralCrossRefGoogle Scholar
  147. Harada, H., Hiraoka, M., & Kizaka-Kondoh, S. (2002). Antitumor effect of TAT-oxygen-dependent degradation-caspase-3 fusion protein specifically stabilized and activated in hypoxic tumor cells. Cancer Research, 62, 2013–2018.PubMedGoogle Scholar
  148. Hariton-Gazal, E., Rosenbluh, J., Graessmann, A., Gilon, C., & Loyter, A. (2003). Direct translocation of histone molecules across cell membranes. Journal of Cell Science, 116, 4577–4586.PubMedCrossRefGoogle Scholar
  149. Harris, T. J., von Maltzahn, G., Lord, M. E., Park, J. H., Agrawal, A., Min, D. H., et al. (2008). Protease-triggered unveiling of bioactive nanoparticles. Small (Weinheim an der Bergstrasse, Germany), 4, 1307–1312.CrossRefGoogle Scholar
  150. Hart, M. R., Su, H. Y., Broka, D., Goverdhan, A., & Schroeder, J. A. (2013). Inactive ERBB receptors cooperate with reactive oxygen species to suppress cancer progression. Molecular Therapy, 21, 1996–2007.PubMedPubMedCentralCrossRefGoogle Scholar
  151. Hatakeyama, H., Akita, H., Ito, E., Hayashi, Y., Oishi, M., Nagasaki, Y., et al. (2011). Systemic delivery of siRNA to tumors using a lipid nanoparticle containing a tumor-specific cleavable PEG-lipid. Biomaterials, 32, 4306–4316.PubMedCrossRefGoogle Scholar
  152. Hayashi, Y., Mizuno, R., Ikramy, K. A., Akita, H., & Harashima, H. (2012). Pretreatment of hepatocyte growth factor gene transfer mediated by octaarginine peptide-modified nanoparticles ameliorates LPS/D-galactosamine-induced hepatitis. Nucleic Acid Therapeutics, 22, 360–363.PubMedPubMedCentralCrossRefGoogle Scholar
  153. Hayashi, Y., Yamauchi, J., Khalil, I. A., Kajimoto, K., Akita, H., & Harashima, H. (2011). Cell penetrating peptide-mediated systemic siRNA delivery to the liver. International Journal of Pharmaceutics, 419, 308–313.PubMedPubMedCentralCrossRefGoogle Scholar
  154. He, H., Sun, L., Ye, J., Liu, E., Chen, S., Liang, Q., et al. (2016). Enzyme-triggered, cell penetrating peptide-mediated delivery of anti-tumor agents. Journal of Controlled Release, 240, 67–76.PubMedCrossRefGoogle Scholar
  155. Held, A., Glas, A., Dietrich, L., Bollmann, M., Brandstadter, K., Grossmann, T. N., et al. (2018). Targeting beta-catenin dependent Wnt signaling via peptidomimetic inhibitors in murine chondrocytes and OA cartilage. Osteoarthritis Cartilage.PubMedCrossRefGoogle Scholar
  156. Herce, H. D., Schumacher, D., Schneider, A. F. L., Ludwig, A. K., Mann, F. A., Fillies, M., et al. (2017). Cell-permeable nanobodies for targeted immunolabelling and antigen manipulation in living cells. Nature Chemistry, 9, 762–771.PubMedCrossRefGoogle Scholar
  157. Herve, F., Ghinea, N., & Scherrmann, J. M. (2008). CNS delivery via adsorptive transcytosis. American Association of Pharmaceutical Scientists Journal, 10, 455–472.PubMedGoogle Scholar
  158. Hida, K., Maishi, N., Sakurai, Y., Hida, Y., & Harashima, H. (2016). Heterogeneity of tumor endothelial cells and drug delivery. Advanced Drug Delivery Reviews, 99, 140–147.PubMedCrossRefGoogle Scholar
  159. Hingorani, D. V., Lemieux, A. J., Acevedo, J. R., Glasgow, H. L., Kedarisetty, S., Whitney, M. A., et al. (2017). Early detection of squamous cell carcinoma in carcinogen induced oral cancer rodent model by ratiometric activatable cell penetrating peptides. Oral Oncology, 71, 156–162.PubMedPubMedCentralCrossRefGoogle Scholar
  160. Hofbauer, A., Peters, J., Arcalis, E., Rademacher, T., Lampel, J., Eudes, F., et al. (2014). The induction of recombinant protein bodies in different subcellular compartments reveals a cryptic plastid-targeting signal in the 27-kDa γ-Zein sequence. Frontiers in Bioengineering and Biotechnology, 2, 67.PubMedPubMedCentralCrossRefGoogle Scholar
  161. Holm, T., Netzereab, S., Hansen, M., Langel, Ü., & Hällbrink, M. (2005). Uptake of cell-penetrating peptides in yeasts. FEBS Letters, 579, 5217–5222.PubMedPubMedCentralCrossRefGoogle Scholar
  162. Hossain, M. K., Cho, H. Y., Kim, K. J., & Choi, J. W. (2015). In situ monitoring of doxorubicin release from biohybrid nanoparticles modified with antibody and cell-penetrating peptides in breast cancer cells using surface-enhanced Raman spectroscopy. Biosensors and Bioelectronics, 71, 300–305.PubMedCrossRefPubMedCentralGoogle Scholar
  163. Hossen, M. N., Kajimoto, K., Akita, H., Hyodo, M., & Harashima, H. (2012). Vascular-targeted nanotherapy for obesity: Unexpected passive targeting mechanism to obese fat for the enhancement of active drug delivery. Journal of Control Release, 163, 101–110.CrossRefGoogle Scholar
  164. Hsu, T., & Mitragotri, S. (2011). Delivery of siRNA and other macromolecules into skin and cells using a peptide enhancer. Proceedings of the National Academy of Sciences USA, 108, 15816–15821.CrossRefGoogle Scholar
  165. Huang, R., Li, J., Kebebe, D., Wu, Y., Zhang, B., & Liu, Z. (2018). Cell penetrating peptides functionalized gambogic acid-nanostructured lipid carrier for cancer treatment. Drug Delivery, 25, 757–765.PubMedPubMedCentralCrossRefGoogle Scholar
  166. Huang, S., Shao, K., Kuang, Y., Liu, Y., Li, J., An, S., et al. (2013a). Tumor targeting and microenvironment-responsive nanoparticles for gene delivery. Biomaterials, 34, 5294–5302.PubMedPubMedCentralCrossRefGoogle Scholar
  167. Huang, S., Shao, K., Liu, Y., Kuang, Y., Li, J., An, S., et al. (2013b). Tumor-targeting and microenvironment-responsive smart nanoparticles for combination therapy of antiangiogenesis and apoptosis. ACS Nano, 7, 2860–2871.PubMedCrossRefGoogle Scholar
  168. Huang, Y., Park, Y. S., Wang, J., Moon, C., Kwon, Y. M., Chung, H. S., et al. (2010). ATTEMPTS system: A macromolecular prodrug strategy for cancer drug delivery. Current Pharmaceutical Design, 16, 2369–2376.PubMedCrossRefGoogle Scholar
  169. Huber, J. D., Egleton, R. D., & Davis, T. P. (2001). Molecular physiology and pathophysiology of tight junctions in the blood-brain barrier. Trends in Neurosciences, 24, 719–725.PubMedCrossRefGoogle Scholar
  170. Hunt, H., Simon-Gracia, L., Tobi, A., Kotamraju, V. R., Sharma, S., Nigul, M., et al. (2017). Targeting of p32 in peritoneal carcinomatosis with intraperitoneal linTT1 peptide-guided pro-apoptotic nanoparticles. Journal of Control Release, 260, 142–153.CrossRefGoogle Scholar
  171. Hussain, T., Mastrodimos, M. B., Raju, S. C., Glasgow, H. L., Whitney, M., Friedman, B., et al. (2015). Fluorescently labeled peptide increases identification of degenerated facial nerve branches during surgery and improves functional outcome. PLoS One, 10.PubMedPubMedCentralCrossRefGoogle Scholar
  172. Hyman, J. M., Geihe, E. I., Trantow, B. M., Parvin, B., & Wender, P. A. (2012). A molecular method for the delivery of small molecules and proteins across the cell wall of algae using molecular transporters. Proceedings of the National Academy of Sciences USA, 109, 13225–13230.CrossRefGoogle Scholar
  173. Hyvonen, M., Enbäck, J., Huhtala, T., Lammi, J., Sihto, H., Weisell, J., et al. (2014). Novel target for peptide-based imaging and treatment of brain tumors. Molecular Cancer Therapeutics, 13, 996–1007.PubMedPubMedCentralCrossRefGoogle Scholar
  174. Hällbrink, M., & Karelson, M. (2015). Prediction of cell-penetrating peptides. Methods Mol Biol, 1324, 39–58.PubMedCrossRefGoogle Scholar
  175. Hällbrink, M., Kilk, K., Elmquist, A., Lundberg, P., Lindgren, M., Jiang, Y., et al. (2005). Prediction of cell-penetrating peptides. International Journal of Peptide Research and Therapeutics, 11, 249–259.CrossRefGoogle Scholar
  176. Hällbrink, M., Kilk, K., Lundberg, P., Soomets, U., Elmquist, A., Zorko, M., et al. (2002). Cell-penetrating peptides. PCT WO2003106491.Google Scholar
  177. Im, J., Das, S., Jeong, D., Kim, C. J., Lim, H. S., Kim, K. H., et al. (2017). Intracellular and transdermal protein delivery mediated by non-covalent interactions with a synthetic guanidine-rich molecular carrier. International Journal of Pharmaceutics, 528, 646–654.PubMedPubMedCentralCrossRefGoogle Scholar
  178. Immordino, M. L., Dosio, F., & Cattel, L. (2006). Stealth liposomes: Review of the basic science, rationale, and clinical applications, existing and potential. International Journal of Nanomedicine, 1, 297–315.PubMedPubMedCentralCrossRefGoogle Scholar
  179. Ishiguro, S., Alhakamy, N. A., Uppalapati, D., Delzeit, J., Berkland, C. J., & Tamura, M. (2017). Combined local pulmonary and systemic delivery of AT2R gene by modified TAT peptide nanoparticles attenuates both murine and human lung carcinoma xenografts in Mice. Journal of Pharmaceutical Sciences, 106, 385–394.PubMedCrossRefGoogle Scholar
  180. Ishikawa, T., Somiya, K., Munechika, R., Harashima, H., & Yamada, Y. (2018). Mitochondrial transgene expression via an artificial mitochondrial DNA vector in cells from a patient with a mitochondrial disease. Journal of Controlled Release.Google Scholar
  181. Iwasaki, T., Tokuda, Y., Kotake, A., Okada, H., Takeda, S., Kawano, T., et al. (2015). Cellular uptake and in vivo distribution of polyhistidine peptides. Journal of Controlled Release, 210, 115–124.PubMedPubMedCentralCrossRefGoogle Scholar
  182. Iwase, Y., Kamei, N., Khafagy el, S., Miyamoto, M., & Takeda-Morishita, M. (2016). Use of a non-covalent cell-penetrating peptide strategy to enhance the nasal delivery of interferon beta and its PEGylated form. International Journal of Pharmaceutics, 510, 304–310.Google Scholar
  183. Jacq, A., Burlat, V., & Jamet, E. (2017). Plant cell wall proteomics as a strategy to reveal candidate proteins involved in extracellular lipid metabolism. Current Protein and Peptide Science.Google Scholar
  184. Jagtap, U. B., Gurav, R. G., & Bapat, V. A. (2011). Role of RNA interference in plant improvement. Die Naturwissenschaften, 98, 473–492.PubMedCrossRefGoogle Scholar
  185. Jain, A., & Chugh, A. (2016). Mitochondrial transit peptide exhibits cell penetration ability and efficiently delivers macromolecules to mitochondria. FEBS Letters, 590, 2896–2905.PubMedPubMedCentralCrossRefGoogle Scholar
  186. Jain, A., Yadav, B. K., & Chugh, A. (2015). Marine antimicrobial peptide tachyplesin as an efficient nanocarrier for macromolecule delivery in plant and mammalian cells. The FEBS Journal, 282, 732–745.PubMedPubMedCentralCrossRefGoogle Scholar
  187. Jain, M., Chauhan, S. C., Singh, A. P., Venkatraman, G., Colcher, D., & Batra, S. K. (2005). Penetratin improves tumor retention of single-chain antibodies: A novel step toward optimization of radioimmunotherapy of solid tumors. Cancer Research, 65, 7840–7846.PubMedCrossRefGoogle Scholar
  188. Jarvinen, T. A., May, U., & Prince, S. (2015). Systemically administered, target organ-specific therapies for regenerative medicine. International Journal of Molecular Sciences, 16, 23556–23571.PubMedPubMedCentralCrossRefGoogle Scholar
  189. Jarvinen, T. A. H., & Ruoslahti, E. (2018). Generation of multi-functional target organ specific anti-fibrotic molecule by molecular engineering of the extracellular matrix protein, decorin. British Journal of Pharmacology.Google Scholar
  190. Jean, S. R., Ahmed, M., Lei, E. K., Wisnovsky, S. P., & Kelley, S. O. (2016). Peptide-mediated delivery of chemical probes and therapeutics to mitochondria. Accounts of Chemical Research, 49, 1893–1902.PubMedCrossRefGoogle Scholar
  191. Jeong, E. J., Choi, M., Lee, J., Rhim, T., & Lee, K. Y. (2015). The spacer arm length in cell-penetrating peptides influences chitosan/siRNA nanoparticle delivery for pulmonary inflammation treatment. Nanoscale, 7, 20095–20104.PubMedCrossRefGoogle Scholar
  192. Jeong, J. H., Kim, K., Lim, D., Jeong, K., Hong, Y., Nguyen, V. H., et al. (2014). Anti-tumoral effect of the mitochondrial target domain of Noxa delivered by an engineered Salmonella typhimurium. PLoS One, 9, e80050.PubMedPubMedCentralCrossRefGoogle Scholar
  193. Jeyarajan, S., Xavier, J., Rao, N. M., & Gopal, V. (2010). Plasmid DNA delivery into MDA-MB-453 cells mediated by recombinant Her-NLS fusion protein. International Journal of Nanomedicine, 5, 725–733.PubMedPubMedCentralGoogle Scholar
  194. Ji, T., Ding, Y., Zhao, Y., Wang, J., Qin, H., Liu, X., et al. (2015). Peptide assembly integration of fibroblast-targeting and cell-penetration features for enhanced antitumor drug delivery. Advanced Materials, 27, 1865–1873.PubMedCrossRefGoogle Scholar
  195. Jiang, T., Olson, E. S., Nguyen, Q. T., Roy, M., Jennings, P. A., & Tsien, R. Y. (2004). Tumor imaging by means of proteolytic activation of cell-penetrating peptides. Proceedings of the National Academy of Sciences USA, 101, 17867–17872.CrossRefGoogle Scholar
  196. Jiang, T., Wang, T., Li, T., Ma, Y., Shen, S., He, B., et al. (2018). Enhanced transdermal drug delivery by transfersome-embedded oligopeptide hydrogel for topical chemotherapy of melanoma. ACS Nano.Google Scholar
  197. Jiang, T., Zhang, Z., Zhang, Y., Lv, H., Zhou, J., Li, C., et al. (2012). Dual-functional liposomes based on pH-responsive cell-penetrating peptide and hyaluronic acid for tumor-targeted anticancer drug delivery. Biomaterials, 33, 9246–9258.PubMedCrossRefGoogle Scholar
  198. Jin, E., Zhang, B., Sun, X., Zhou, Z., Ma, X., Sun, Q., et al. (2013). Acid-active cell-penetrating peptides for in vivo tumor-targeted drug delivery. Journal of the American Chemical Society, 135, 933–940.PubMedCrossRefGoogle Scholar
  199. Jo, E., Heo, J. S., Lim, J. Y., Lee, B. R., Yoon, C. J., Kim, J., et al. (2018). Peptide ligand-mediated endocytosis of nanoparticles to cancer cells: Cell receptor-binding- versus cell membrane-penetrating peptides. Biotechnology and Bioengineering.Google Scholar
  200. Johnson, L. N., Cashman, S. M., Read, S. P., & Kumar-Singh, R. (2010). Cell penetrating peptide POD mediates delivery of recombinant proteins to retina, cornea and skin. Vision Research, 50, 686–697.PubMedCrossRefGoogle Scholar
  201. Juks, C., Padari, K., Margus, H., Kriiska, A., Etverk, I., Arukuusk, P., et al. (2015). The role of endocytosis in the uptake and intracellular trafficking of PepFect14-nucleic acid nanocomplexes via class A scavenger receptors. Biochimica et Biophysica Acta (BBA)-Biomembranes, 12, 25.Google Scholar
  202. Jun, H. R., Pham, C. D., Lim, S. I., Lee, S. C., Kim, Y. S., Park, S., et al. (2010). An RNA-hydrolyzing recombinant antibody exhibits an antiviral activity against classical swine fever virus. Biochemical and Biophysical Research Communications, 395, 484–489.PubMedCrossRefGoogle Scholar
  203. Kagawa, Y., Inoki, Y., & Endo, H. (2001). Gene therapy by mitochondrial transfer. Advanced Drug Delivery Reviews, 49, 107–119.PubMedCrossRefGoogle Scholar
  204. Kalafut, D., Anderson, T. N., & Chmielewski, J. (2012). Mitochondrial targeting of a cationic amphiphilic polyproline helix. Bioorganic and Medicinal Chemistry Letters, 22, 561–563.PubMedCrossRefGoogle Scholar
  205. Kamei, N., Khafagy, E. S., Hirose, J. & Takeda-Morishita, M. (2017a). Potential of single cationic amino acid molecule “Arginine” for stimulating oral absorption of insulin. International Journal of Pharmaceutics, 18, 30075-3.Google Scholar
  206. Kamei, N., Nielsen, E. J., Khafagy el, S., & Takeda-Morishita, M. (2013). Noninvasive insulin delivery: The great potential of cell-penetrating peptides. Therapeutic Delivery, 4, 315–326.Google Scholar
  207. Kamei, N., & Takeda-Morishita, M. (2015). Brain delivery of insulin boosted by intranasal coadministration with cell-penetrating peptides. Journal of Controlled Release, 197, 105–110.PubMedCrossRefGoogle Scholar
  208. Kamei, N., Tanaka, M., Choi, H., Okada, N., Ikeda, T., Itokazu, R., et al. (2017b). Effect of an enhanced nose-to-brain delivery of insulin on mild and progressive memory loss in the senescence-accelerated mouse. Molecular Pharmaceutics, 14, 916–927.PubMedCrossRefGoogle Scholar
  209. Kamei, N., Yamaoka, A., Fukuyama, Y., Itokazu, R., & Takeda-Morishita, M. (2018). Noncovalent strategy with cell-penetrating peptides to facilitate the brain delivery of insulin through the blood-brain barrier. Biological and Pharmaceutical Bulletin, 41, 546–554.PubMedCrossRefGoogle Scholar
  210. Kanazawa, T. (2015). Brain delivery of small interfering ribonucleic acid and drugs through intranasal administration with nano-sized polymer micelles. Medical devices (Auckland, NZ), 8, 57–64.Google Scholar
  211. Kanazawa, T., Akiyama, F., Kakizaki, S., Takashima, Y., & Seta, Y. (2013). Delivery of siRNA to the brain using a combination of nose-to-brain delivery and cell-penetrating peptide-modified nano-micelles. Biomaterials, 34, 9220–9226.PubMedCrossRefGoogle Scholar
  212. Kanazawa, T., Morisaki, K., Suzuki, S., & Takashima, Y. (2014). Prolongation of life in rats with malignant glioma by intranasal siRNA/drug codelivery to the brain with cell-penetrating peptide-modified micelles. Molecular Pharmaceutics, 11, 1471–1478.PubMedCrossRefGoogle Scholar
  213. Kang, Y. C., Son, M., Kang, S., Im, S., Piao, Y., Lim, K. S., et al. (2018). Cell-penetrating artificial mitochondria-targeting peptide-conjugated metallothionein 1A alleviates mitochondrial damage in Parkinson’s disease models. Experimental & Molecular Medicine, 50, 105.CrossRefGoogle Scholar
  214. Kastin, A. J., & Pan, W. (2016). Involvement of the blood-brain barrier in metabolic regulation. CNS & Neurological Disorders-Drug Targets, 15, 1118–1128.CrossRefGoogle Scholar
  215. Kawabata, A., Baoum, A., Ohta, N., Jacquez, S., Seo, G. M., Berkland, C., et al. (2012). Intratracheal administration of a nanoparticle-based therapy with the angiotensin II type 2 receptor gene attenuates lung cancer growth. Cancer Research, 72, 2057–2067.PubMedPubMedCentralCrossRefGoogle Scholar
  216. Ke, A. Q., Liu, A. D., Gao, Y. N., Luo, D. N., Li, Z. F., Yu, Y. Q., et al. (2018). Development of novel affinity reagents for detecting protein tyrosine phosphorylation based on superbinder SH2 domain in tumor cells. Analytica Chimica Acta, 1032, 138–146.PubMedCrossRefGoogle Scholar
  217. Ke, W., Shao, K., Huang, R., Han, L., Liu, Y., Li, J., et al. (2009). Gene delivery targeted to the brain using an Angiopep-conjugated polyethyleneglycol-modified polyamidoamine dendrimer. Biomaterials, 30, 6976–6985.PubMedCrossRefGoogle Scholar
  218. Khafagy el, S., Iwamae, R., Kamei, N., & Takeda-Morishita, M. (2015). Region-dependent role of cell-penetrating peptides in insulin absorption across the rat small intestinal membrane. The AAPS journal, 17, 1427–1437.Google Scholar
  219. Khafagy el, S., Morishita, M., Isowa, K., Imai, J., & Takayama, K. (2009). Effect of cell-penetrating peptides on the nasal absorption of insulin. Journal of Controlled Release, 133, 103–108.Google Scholar
  220. Khalil, I. A., Hayashi, Y., Mizuno, R., & Harashima, H. (2011). Octaarginine- and pH sensitive fusogenic peptide-modified nanoparticles for liver gene delivery. Journal of Controlled Release, 156, 374–380.PubMedPubMedCentralCrossRefGoogle Scholar
  221. Khalily, M. P., Gerekci, S., Gulec, E. A., Ozen, C., & Ozcubukcu, S. (2018). Structure-based design, synthesis and anticancer effect of cyclic Smac-polyarginine peptides. Amino Acids.Google Scholar
  222. Khan, A. R., Liu, M., Khan, M. W., & Zhai, G. (2017). Progress in brain targeting drug delivery system by nasal route. Journal of Controlled Release, 5, 30825–30828.Google Scholar
  223. Kim, B. K., Kang, H., Doh, K. O., Lee, S. H., Park, J. W., Lee, S. J., et al. (2012). Homodimeric SV40 NLS peptide formed by disulfide bond as enhancer for gene delivery. Bioorganic & Medicinal Chemistry Letters, 22, 5415–5418.CrossRefGoogle Scholar
  224. Kim, G. C., Ahn, J. H., Oh, J. H., Nam, S., Hyun, S., Yu, J., et al. (2018a). Photoswitching of cell penetration of amphipathic peptides by control of alpha-helical conformation. Biomacromolecules.Google Scholar
  225. Kim, J. S., Park, J. Y., Shin, S. M., Park, S. W., Jun, S. Y., Hong, J. S., et al. (2018b). Engineering of a tumor cell-specific, cytosol-penetrating antibody with high endosomal escape efficacy. Biochemical and Biophysical Research Communications, 503, 2510–2516.PubMedCrossRefGoogle Scholar
  226. Kim, Y., Lillo, A. M., Steiniger, S. C., Liu, Y., Ballatore, C., Anichini, A., et al. (2006). Targeting heat shock proteins on cancer cells: Selection, characterization, and cell-penetrating properties of a peptidic GRP78 ligand. Biochemistry, 45, 9434–9444.PubMedPubMedCentralCrossRefGoogle Scholar
  227. Kim, Y. H., Han, M. E., & Oh, S. O. (2017). The molecular mechanism for nuclear transport and its application. Anatomy & Cell Biology, 50, 77–85.CrossRefGoogle Scholar
  228. Kimura, S., Kawano, T., & Iwasaki, T. (2017). Short polyhistidine peptides penetrate effectively into Nicotiana tabacum-cultured cells and Saccharomyces cerevisiae cells. Bioscience, Biotechnology, and Biochemistry, 81, 112–118.PubMedPubMedCentralCrossRefGoogle Scholar
  229. Kobayashi, N., Niwa, M., Hao, Y., & Yoshida, T. (2010). Nucleolar localization signals of LIM kinase 2 function as a cell-penetrating peptide. Protein and Peptide Letters, 17, 1480–1488.PubMedPubMedCentralCrossRefGoogle Scholar
  230. Kreuter, J., Hekmatara, T., Dreis, S., Vogel, T., Gelperina, S., & Langer, K. (2007). Covalent attachment of apolipoprotein A-I and apolipoprotein B-100 to albumin nanoparticles enables drug transport into the brain. Journal of Controlled Release, 118, 54–58.PubMedCrossRefGoogle Scholar
  231. Kristensen, M., Birch, D., & Mörck Nielsen, H. (2016). Applications and challenges for use of cell-penetrating peptides as delivery vectors for peptide and protein cargos. International Journal of Molecular Sciences, 17, pii: E185.Google Scholar
  232. Kumagai, A. K., Eisenberg, J. B., & Pardridge, W. M. (1987). Absorptive-mediated endocytosis of cationized albumin and a beta-endorphin-cationized albumin chimeric peptide by isolated brain capillaries. Model system of blood-brain barrier transport. Journal of Biological Chemistry, 262, 15214–15219.PubMedGoogle Scholar
  233. Kumar, P., Ban, H. S., Kim, S. S., Wu, H., Pearson, T., Greiner, D. L., et al. (2008). T cell-specific siRNA delivery suppresses HIV-1 infection in humanized mice. Cell, 134, 577–586.PubMedPubMedCentralCrossRefGoogle Scholar
  234. Kumar, P., Wu, H., McBride, J. L., Jung, K. E., Kim, M. H., Davidson, B. L., et al. (2007). Transvascular delivery of small interfering RNA to the central nervous system. Nature, 448, 39–43.PubMedPubMedCentralCrossRefGoogle Scholar
  235. Kumar, S., Narishetty, S. T., & Tummala, H. (2015a). Peptides as skin penetration enhancers for low molecular weight drugs and macromolecules. In N. Dragicevic & H. I. Maibach (Eds.) Percutaneous penetration enhancers chemical methods in penetration enhancement: Modification of the Stratum Corneum. Heidelberg: Springer.Google Scholar
  236. Kumar, S., Sahdev, P., Perumal, O., & Tummala, H. (2012). Identification of a novel skin penetration enhancement peptide by phage display peptide library screening. Molecular Pharmaceutics, 9, 1320–1330.PubMedPubMedCentralCrossRefGoogle Scholar
  237. Kumar, S., Zakrewsky, M., Chen, M., Menegatti, S., Muraski, J. A., & Mitragotri, S. (2015b). Peptides as skin penetration enhancers: Mechanisms of action. Journal of Controlled Release, 199, 168–178.PubMedCrossRefGoogle Scholar
  238. Kumaraswamy, A., Mamidi, A., Desai, P., Sivagnanam, A., Revathi Perumalsamy, L., Ramakrishnan, C., Gromiha, M., et al. (2018). The non-enzymatic RAS effector RASSF7 inhibits oncogenic c-Myc function. Journal of Biological Chemistry.Google Scholar
  239. Kurzrock, R., Gabrail, N., Chandhasin, C., Moulder, S., Smith, C., Brenner, A., et al. (2012). Safety, pharmacokinetics, and activity of GRN1005, a novel conjugate of angiopep-2, a peptide facilitating brain penetration, and paclitaxel, in patients with advanced solid tumors. Molecular Cancer Therapeutics, 11, 308–316.PubMedCrossRefGoogle Scholar
  240. Kusumoto, K., Akita, H., Ishitsuka, T., Matsumoto, Y., Nomoto, T., Furukawa, R., et al. (2013). Lipid envelope-type nanoparticle incorporating a multifunctional peptide for systemic siRNA delivery to the pulmonary endothelium. ACS Nano, 7, 7534–7541.CrossRefGoogle Scholar
  241. Kwon, K. C., & Daniell, H. (2016). Oral delivery of protein drugs bioencapsulated in plant cells. Molecular Therapy, 24, 1342–1350.PubMedPubMedCentralCrossRefGoogle Scholar
  242. Laakkonen, P., Porkka, K., Hoffman, J. A., & Ruoslahti, E. (2002). A tumor-homing peptide with a targeting specificity related to lymphatic vessels. Nature Medicine, 8, 751–755.CrossRefGoogle Scholar
  243. Lakkadwala, S., & Singh, J. (2018). Dual functionalized 5-fluorouracil liposomes as highly efficient nanomedicine for glioblastoma treatment as assessed in an in vitro brain tumor model. Journal of Pharmaceutical Sciences.Google Scholar
  244. Lakshmanan, M., Kodama, Y., Yoshizumi, T., Sudesh, K., & Numata, K. (2013). Rapid and efficient gene delivery into plant cells using designed peptide carriers. Biomacromolecules, 14, 10–16.PubMedCrossRefGoogle Scholar
  245. Lam, J. K., Liang, W., & Chan, H. K. (2012). Pulmonary delivery of therapeutic siRNA. Advanced Drug Delivery Reviews, 64, 1–15.PubMedCrossRefGoogle Scholar
  246. Larue, B., Hogg, E., Sagare, A., Jovanovic, S., Maness, L., Maurer, C., et al. (2004). Method for measurement of the blood-brain barrier permeability in the perfused mouse brain: Application to amyloid-beta peptide in wild type and Alzheimer’s Tg2576 mice. Journal of Neuroscience Methods, 138, 233–242.PubMedCrossRefGoogle Scholar
  247. Lee, E. S., Gao, Z., Kim, D., Park, K., Kwon, I. C., & Bae, Y. H. (2008a). Super pH-sensitive multifunctional polymeric micelle for tumor pH(e) specific TAT exposure and multidrug resistance. Journal of Controlled Release, 129, 228–236.PubMedPubMedCentralCrossRefGoogle Scholar
  248. Lee, H. S., Park, C. B., Kim, J. M., Jang, S. A., Park, I. Y., Kim, M. S., et al. (2008b). Mechanism of anticancer activity of buforin IIb, a histone H2A-derived peptide. Cancer Letters, 271, 47–55.PubMedPubMedCentralCrossRefGoogle Scholar
  249. Lee, W. R., Jang, J. Y., Kim, J. S., Kwon, M. H., & Kim, Y. S. (2010). Gene silencing by cell-penetrating, sequence-selective and nucleic-acid hydrolyzing antibodies. Nucleic Acids Research, 38, 1596–1609.PubMedCrossRefGoogle Scholar
  250. Lei, E. K., & Kelley, S. O. (2017). Delivery and release of small-molecule probes in mitochondria using traceless linkers. Journal of the American Chemical Society, 139, 9455–9458.PubMedCrossRefGoogle Scholar
  251. Letoha, T., Kusz, E., Papai, G., Szabolcs, A., Kaszaki, J., Varga, I., et al. (2006). In vitro and in vivo nuclear factor-kappaB inhibitory effects of the cell-penetrating penetratin peptide. Molecular Pharmacology, 69, 2027–2036.PubMedCrossRefGoogle Scholar
  252. Li, H., He, J., Yi, H., Xiang, G., Chen, K., et al. (2015). siRNA suppression of hTERT using activatable cell-penetrating peptides in hepatoma cells. Bioscience Reports, 35.CrossRefGoogle Scholar
  253. Li, L., Geisler, I., Chmielewski, J., & Cheng, J. X. (2010). Cationic amphiphilic polyproline helix P11LRR targets intracellular mitochondria. Journal of Controlled Release, 142, 259–266.PubMedCrossRefGoogle Scholar
  254. Li, T., Bourgeois, J. P., Celli, S., Glacial, F., le Sourd, A. M., Mecheri, S., et al. (2012). Cell-penetrating anti-GFAP VHH and corresponding fluorescent fusion protein VHH-GFP spontaneously cross the blood-brain barrier and specifically recognize astrocytes: Application to brain imaging. The FASEB Journal, 26, 3969–3979.PubMedCrossRefGoogle Scholar
  255. Li, X., Tsibouklis, J., Weng, T., Zhang, B., Yin, G., Feng, G., et al. (2017). Nano carriers for drug transport across the blood-brain barrier. Journal of Drug Targeting, 25, 17–28.PubMedCrossRefGoogle Scholar
  256. Lightowlers, R. N., Taylor, R. W., & Turnbull, D. M. (2015). Mutations causing mitochondrial disease: What is new and what challenges remain? Science, 349, 1494–1499.PubMedCrossRefGoogle Scholar
  257. Lim, K. J., Sung, B. H., Shin, J. R., Lee, Y. W., Kim DA, J., Yang, K. S., et al. (2013). A cancer specific cell-penetrating peptide, BR2, for the efficient delivery of an scFv into cancer cells. PLoS One, 8, e66084.PubMedPubMedCentralCrossRefGoogle Scholar
  258. Lin, C. M., Huang, K., Zeng, Y., Chen, X. C., Wang, S., & Li, Y. (2012). A simple, noninvasive and efficient method for transdermal delivery of siRNA. Archives of Dermatological Research, 304, 139–144.PubMedCrossRefGoogle Scholar
  259. Lin, R., Zhang, P., Cheetham, A. G., Walston, J., Abadir, P., & Cui, H. (2015). Dual peptide conjugation strategy for improved cellular uptake and mitochondria targeting. Bioconjugate Chemistry, 26, 71–77.PubMedPubMedCentralCrossRefGoogle Scholar
  260. Lin, S. Y., Chen, N. T., Sum, S. P., Lo, L. W., & Yang, C. S. (2008). Ligand exchanged photoluminescent gold quantum dots functionalized with leading peptides for nuclear targeting and intracellular imaging. Chemical Communications, 21, 4762–4764.CrossRefGoogle Scholar
  261. Lin, T., Liu, E., He, H., Shin, M. C., Moon, C., Yang, V. C., et al. (2016a). Nose-to-brain delivery of macromolecules mediated by cell-penetrating peptides. Acta Pharmaceutica Sinica B, 6, 352–358.PubMedPubMedCentralCrossRefGoogle Scholar
  262. Lin, T., Zhao, P., Jiang, Y., Tang, Y., Jin, H., Pan, Z., et al. (2016b). Blood-brain-barrier-penetrating albumin nanoparticles for biomimetic drug delivery via albumin-binding protein pathways for antiglioma therapy. ACS Nano, 10, 9999–10012.PubMedCrossRefGoogle Scholar
  263. Lindgren, M. E., Hällbrink, M. M., Elmquist, A. M., & Langel, Ü. (2004). Passage of cell-penetrating peptides across a human epithelial cell layer in vitro. Biochemical Journal, 377, 69–76.PubMedPubMedCentralCrossRefGoogle Scholar
  264. Lippmann, E. S., Azarin, S. M., Kay, J. E., Nessler, R. A., Wilson, H. K., Al-Ahmad, A., et al. (2012). Derivation of blood-brain barrier endothelial cells from human pluripotent stem cells. Nature Biotechnology, 30, 783–791.PubMedPubMedCentralCrossRefGoogle Scholar
  265. Liu, B. R., Chou, J. C., & Lee, H. J. (2008). Cell membrane diversity in noncovalent protein transduction. Journal of Membrane Biology, 222, 1–15.PubMedCrossRefGoogle Scholar
  266. Liu, B. R., Huang, Y. W., Aronstam, R. S., & Lee, H. J. (2016). Identification of a short cell-penetrating peptide from bovine lactoferricin for intracellular delivery of DNA in human A549 cells. PLoS One, 11.Google Scholar
  267. Liu, C., Liu, X. N., Wang, G. L., Hei, Y., Meng, S., Yang, L. F., et al. (2017a). A dual-mediated liposomal drug delivery system targeting the brain: rational construction, integrity evaluation across the blood-brain barrier, and the transporting mechanism to glioma cells. International Journal of Nanomedicine, 12, 2407–2425.PubMedPubMedCentralCrossRefGoogle Scholar
  268. Liu, C., Yao, S., Li, X., Wang, F., & Jiang, Y. (2017b). iRGD-mediated core-shell nanoparticles loading carmustine and O6-benzylguanine for glioma therapy. Journal of Drug Targeting, 25, 235–246.PubMedCrossRefGoogle Scholar
  269. Liu, D., Zienkiewicz, J., Digiandomenico, A., & Hawiger, J. (2009a). Suppression of acute lung inflammation by intracellular peptide delivery of a nuclear import inhibitor. Molecular Therapy, 17, 796–802.PubMedPubMedCentralCrossRefGoogle Scholar
  270. Liu, J., Zhang, B., Luo, Z., Ding, X., Li, J., Dai, L., et al. (2015). Enzyme responsive mesoporous silica nanoparticles for targeted tumor therapy in vitro and in vivo. Nanoscale, 7, 3614–3626.PubMedCrossRefGoogle Scholar
  271. Liu, M.-J., Chou, J.-C., & Lee, H.-J. (2013). A gene delivery method mediated by three arginine-rich cell-penetrating peptides in plant cells. Advanced Studies in Biology, 5, 71–88.CrossRefGoogle Scholar
  272. Liu, X., Jiang, J., Nel, A. E., & Meng, H. (2017c). Major effect of transcytosis on nano drug delivery to pancreatic cancer. Molecular & Cellular Oncology, 4.Google Scholar
  273. Liu, X., Wang, Y., & Hnatowich, D. J. (2011). A nanoparticle for tumor targeted delivery of oligomers. Methods Mol Biol, 764, 91–105.PubMedCrossRefGoogle Scholar
  274. Liu, X., Wang, Y., Nakamura, K., Kawauchi, S., Akalin, A., Cheng, D., et al. (2009b). Auger radiation-induced, antisense-mediated cytotoxicity of tumor cells using a 3-component streptavidin-delivery nanoparticle with 111In. Journal of Nuclear Medicine, 50, 582–590.PubMedCrossRefGoogle Scholar
  275. Liu, Y., He, X., Kuang, Y., An, S., Wang, C., Guo, Y., et al. (2014). A bacteria deriving peptide modified dendrigraft poly-l-lysines (DGL) self-assembling nanoplatform for targeted gene delivery. Molecular Pharmaceutics, 11, 3330–3341.PubMedCrossRefGoogle Scholar
  276. Lodish, H., Berk, A., Kaiser, C., Krieger, M., Scott, M., Bretscher, A., et al. (2007). Molecular cell biology (6th ed.) New York: W. H. Freeman and Company.Google Scholar
  277. Lodish, H., Berk, A., & Zipursky, S. (2000). Overview of the secretory pathway. In Molecular cell biology (4th ed.) New York: W. H. Freeman; 2000 section 17.3. Available from:
  278. Lohcharoenkal, W., Manosaroi, A., Gotz, F., Werner, R. G., Manosroi, W., & Manosaroi, J. (2011). Potent enhancement of GFP uptake into HT-29 cells and rat skin permeation by coincubation with tat peptide. Journal of Pharmaceutical Sciences, 100, 4766–4773.PubMedCrossRefGoogle Scholar
  279. Long, C., Amoasii, L., Mireault, A. A., McAnally, J. R., Li, H., Sanchez-Ortiz, E., et al. (2016). Postnatal genome editing partially restores dystrophin expression in a mouse model of muscular dystrophy. Science, 351, 400–403.PubMedCrossRefGoogle Scholar
  280. Lu, S. W., Hu, J. W., Liu, B. R., Lee, C. Y., Li, J. F., Chou, J. C., et al. (2010). Arginine-rich intracellular delivery peptides synchronously deliver covalently and noncovalently linked proteins into plant cells. Journal of Agricultural and Food Chemistry, 58, 2288–2294.PubMedCrossRefGoogle Scholar
  281. Ludtke, J. J., Zhang, G., Sebestyen, M. G., & Wolff, J. A. (1999). A nuclear localization signal can enhance both the nuclear transport and expression of 1 kb DNA. Journal of Cell Science, 112, 2033–2041.PubMedGoogle Scholar
  282. Lukacs, G. L., Haggie, P., Seksek, O., Lechardeur, D., Freedman, N., & Verkman, A. S. (2000). Size-dependent DNA mobility in cytoplasm and nucleus. Journal of Biological Chemistry, 275, 1625–1629.PubMedCrossRefPubMedCentralGoogle Scholar
  283. Luque-Ortega, J. R., Van’t Hof, W., Veerman, E. C., Saugar, J. M., & Rivas, L. (2008). Human antimicrobial peptide histatin 5 is a cell-penetrating peptide targeting mitochondrial ATP synthesis in Leishmania. The FASEB Journal, 22, 1817–1828.Google Scholar
  284. Lönn, P., Kacsinta, A. D., Cui, X. S., Hamil, A. S., Kaulich, M., Gogoi, K., et al. (2016). Enhancing endosomal escape for intracellular delivery of macromolecular biologic therapeutics. Scientific Reports, 6.Google Scholar
  285. Ma, X. C., Liu, P., Zhang, X. L., Jiang, W. H., Jia, M., Wang, C. X., et al. (2016). Intranasal delivery of recombinant AAV containing BDNF fused with HA2TAT: A potential promising therapy strategy for major depressive disorder. Scientific Reports, 6.Google Scholar
  286. Macdougall, G., Anderton, R. S., Edwards, A. B., Knuckey, N. W., & Meloni, B. P. (2017). The neuroprotective peptide poly-arginine-12 (R12) reduces cell surface levels of NMDA NR2B receptor subunit in cortical neurons; Investigation into the involvement of endocytic mechanisms. Journal of Molecular Neuroscience, 61, 235–246.PubMedCrossRefGoogle Scholar
  287. Mahmood, A., & Bernkop-Schnurch, A. (2018). SEDDS: A game changing approach for the oral administration of hydrophilic macromolecular drugs. Advanced Drug Delivery Reviews.Google Scholar
  288. Mahmood, A., Prufert, F., Efiana, N. A., Ashraf, M. I., Hermann, M., Hussain, S., et al. (2016). Cell-penetrating self-nanoemulsifying drug delivery systems (SNEDDS) for oral gene delivery. Expert Opinion on Drug Delivery, 13, 1503–1512.PubMedCrossRefGoogle Scholar
  289. Mallick, S., Thuy, L. T., Lee, S., Park, J. I., & Choi, J. S. (2018). Liposomes containing cholesterol and mitochondria-penetrating peptide (MPP) for targeted delivery of antimycin A to A549 cells. Colloids Surf B Biointerfaces, 161, 356–364.PubMedCrossRefGoogle Scholar
  290. Manosroi, A., Tangjai, T., Sutthiwanjampa, C., Manosroi, W., Werner, R. G., Gotz, F., et al. (2016). Hypoglycemic activity and stability enhancement of human insulin-tat mixture loaded in elastic anionic niosomes. Drug Delivery, 23, 3157–3167.PubMedCrossRefGoogle Scholar
  291. Manosroi, J., Lohcharoenkal, W., Gotz, F., Werner, R. G., Manosroi, W., & Manosroi, A. (2014). Novel application of polioviral capsid: development of a potent and prolonged oral calcitonin using polioviral binding ligand and Tat peptide. Drug Development and Industrial Pharmacy, 40, 1092–1100.CrossRefGoogle Scholar
  292. Marinova, Z., Vukojevic, V., Surcheva, S., Yakovleva, T., Cebers, G., Pasikova, N., et al. (2005). Translocation of dynorphin neuropeptides across the plasma membrane. A putative mechanism of signal transmission. Journal of Biological Chemistry, 280, 26360–26370.CrossRefGoogle Scholar
  293. Martin, R. M., Herce, H. D., Ludwig, A. K., & Cardoso, M. C. (2016). Visualization of the nucleolus in living cells with cell-penetrating fluorescent peptides. Methods Mol Biol, 3792-9_6.Google Scholar
  294. Martin, R. M., Tunnemann, G., Leonhardt, H., & Cardoso, M. C. (2007). Nucleolar marker for living cells. Histochemistry and Cell Biology, 127, 243–251.PubMedCrossRefGoogle Scholar
  295. McCaffrey, J., McCrudden, C. M., Ali, A. A., Massey, A. S., McBride, J. W., McCrudden, M. T., et al. (2016). Transcending epithelial and intracellular biological barriers; a prototype DNA delivery device. Journal of Controlled Release, 226, 238–247.PubMedCrossRefGoogle Scholar
  296. McCusker, C. T., Wang, Y., Shan, J., Kinyanjui, M. W., Villeneuve, A., Michael, H., et al. (2007). Inhibition of experimental allergic airways disease by local application of a cell-penetrating dominant-negative STAT-6 peptide. The Journal of Immunology, 179, 2556–2564.PubMedCrossRefGoogle Scholar
  297. McGowan, J. W., Shao, Q., Vig, P. J., & Bidwell, G. L., III (2016a). Intranasal administration of elastin-like polypeptide for therapeutic delivery to the central nervous system. Drug Design, Development and Therapy, 10, 2803–2813.Google Scholar
  298. McGowan, J. W., Shao, Q., Vig, P. J., & Bidwell, G. L., III (2016b). Intranasal administration of elastin-like polypeptide for therapeutic delivery to the central nervous system. Drug Design, Development and Therapy, 10, 2803–2813.Google Scholar
  299. Mecham, R. P. (1991). Receptors for laminin on mammalian cells. The FASEB Journal, 5, 2538–2546.PubMedCrossRefGoogle Scholar
  300. Mei, L., Zhang, Q., Yang, Y., He, Q., & Gao, H. (2014). Angiopep-2 and activatable cell penetrating peptide dual modified nanoparticles for enhanced tumor targeting and penetrating. International Journal of Pharmaceutics, 474, 95–102.PubMedPubMedCentralCrossRefGoogle Scholar
  301. Meikle, P. J., Hopwood, J. J., Clague, A. E., & Carey, W. F. (1999). Prevalence of lysosomal storage disorders. JAMA, 281, 249–254.PubMedCrossRefGoogle Scholar
  302. Melnick, A. (2007). Targeting aggressive B-cell lymphomas with cell-penetrating peptides. Biochemical Society Transactions, 35, 802–806.PubMedCrossRefGoogle Scholar
  303. Menegatti, S., Zakrewsky, M., Kumar, S., de Oliveira, J. S., Muraski, J. A., & Mitragotri, S. (2016). De Novo design of skin-penetrating peptides for enhanced transdermal delivery of peptide drugs. Advanced Healthcare Materials, 5, 602–609.PubMedCrossRefGoogle Scholar
  304. Metildi, C. A., Felsen, C. N., Savariar, E. N., Nguyen, Q. T., Kaushal, S., Hoffman, R. M., et al. (2015). Ratiometric activatable cell-penetrating peptides label pancreatic cancer, enabling fluorescence-guided surgery, which reduces metastases and recurrence in orthotopic mouse models. Annals of Surgical Oncology, 22, 2082–2087.PubMedPubMedCentralCrossRefGoogle Scholar
  305. Miyata, K., Ukawa, M., Mohri, K., Fujii, K., Yamada, M., Tanishita, S., et al. (2018). Biocompatible polymers modified with d-octaarginine as an absorption enhancer for nasal peptide delivery. Bioconjugate Chemistry.PubMedCrossRefGoogle Scholar
  306. Mizuno, T., Miyashita, M., & Miyagawa, H. (2009). Cellular internalization of arginine-rich peptides into tobacco suspension cells: A structure-activity relationship study. Journal of Peptide Science, 15, 259–263.PubMedCrossRefGoogle Scholar
  307. Mohammed, Y., Teixido, M., Namjoshi, S., Giralt, E., & Benson, H. (2016). Cyclic dipeptide shuttles as a novel skin penetration enhancement approach: Preliminary evaluation with diclofenac. PLoS One, 11.Google Scholar
  308. Mohri, K., Miyata, K., Egawa, T., Tanishita, S., Endo, R., Yagi, H., et al. (2018). Effects of the chemical structures of oligoarginines conjugated to biocompatible polymers as a mucosal adjuvant on antibody induction in nasal cavities. Chemical and Pharmaceutical Bulletin (Tokyo), 66, 375–381.CrossRefGoogle Scholar
  309. Mok, H., Bae, K. H., Ahn, C. H., & Park, T. G. (2009). PEGylated and MMP-2 specifically dePEGylated quantum dots: Comparative evaluation of cellular uptake. Langmuir, 25, 1645–1650.PubMedCrossRefGoogle Scholar
  310. Moktan, S., Perkins, E., Kratz, F., & Raucher, D. (2012). Thermal targeting of an acid-sensitive doxorubicin conjugate of elastin-like polypeptide enhances the therapeutic efficacy compared with the parent compound in vivo. Molecular Cancer Therapeutics, 11, 1547–1556.PubMedPubMedCentralCrossRefGoogle Scholar
  311. Moktan, S., & Raucher, D. (2012). Anticancer activity of proapoptotic peptides is highly improved by thermal targeting using elastin-like polypeptides. International Journal of Peptide Research and Therapeutics, 18, 227–237.PubMedPubMedCentralCrossRefGoogle Scholar
  312. Montrose, K., Yang, Y., & Krissansen, G. W. (2014). The tetrapeptide core of the carrier peptide Xentry is cell-penetrating: Novel activatable forms of Xentry. Scientific Reports, 4, 4900.PubMedPubMedCentralCrossRefGoogle Scholar
  313. Montrose, K., Yang, Y., Sun, X., Wiles, S., & Krissansen, G. W. (2013). Xentry, a new class of cell-penetrating peptide uniquely equipped for delivery of drugs. Scientific Reports, 3, 1661.PubMedPubMedCentralCrossRefGoogle Scholar
  314. Morales, J. O., Fathe, K. R., Brunaugh, A., Ferrati, S., Li, S., Montenegro-Nicolini, M., et al. (2017). Challenges and future prospects for the delivery of biologics: Oral mucosal, pulmonary, and transdermal routes. The AAPS Journal, 19, 652–668.PubMedCrossRefGoogle Scholar
  315. Morishita, M., Kamei, N., Ehara, J., Isowa, K., & Takayama, K. (2007). A novel approach using functional peptides for efficient intestinal absorption of insulin. Journal of Controlled Release, 118, 177–184.PubMedCrossRefGoogle Scholar
  316. Morris, M. C., Vidal, P., Chaloin, L., Heitz, F., & Divita, G. (1997). A new peptide vector for efficient delivery of oligonucleotides into mammalian cells. Nucleic Acids Research, 25, 2730–2736.PubMedPubMedCentralCrossRefGoogle Scholar
  317. Moschos, S. A., Jones, S. W., Perry, M. M., Williams, A. E., Erjefalt, J. S., Turner, J. J., et al. (2007a). Lung delivery studies using siRNA conjugated to TAT(48-60) and penetratin reveal peptide induced reduction in gene expression and induction of innate immunity. Bioconjugate Chemistry, 18, 1450–1459.PubMedPubMedCentralCrossRefGoogle Scholar
  318. Moschos, S. A., Williams, A. E., & Lindsay, M. A. (2007b). Cell-penetrating-peptide-mediated siRNA lung delivery. Biochem Soc Trans, 35, 807–810.PubMedCrossRefGoogle Scholar
  319. Mourtada, R., Fonseca, S. B., Wisnovsky, S. P., Pereira, M. P., Wang, X., Hurren, R., et al. (2013). Re-directing an alkylating agent to mitochondria alters drug target and cell death mechanism. PLoS One, 8.Google Scholar
  320. Muller, R., Misund, K., Holien, T., Bachke, S., Gilljam, K. M., Vatsveen, T. K., et al. (2013). Targeting proliferating cell nuclear antigen and its protein interactions induces apoptosis in multiple myeloma cells. PLoS One, 8, e70430.PubMedPubMedCentralCrossRefGoogle Scholar
  321. Muller, S., Zhao, Y., Brown, T. L., Morgan, A. C., & Kohler, H. (2005). TransMabs: Cell-penetrating antibodies, the next generation. Expert Opinion on Biological Therapy, 5, 237–241.PubMedCrossRefGoogle Scholar
  322. Muto, K., Kamei, N., Yoshida, M., Takayama, K., & Takeda-Morishita, M. (2016). Cell-penetrating peptide penetratin as a potential tool for developing effective nasal vaccination systems. Journal of Pharmaceutical Sciences, 105, 2014–2017.PubMedPubMedCentralCrossRefGoogle Scholar
  323. Myrberg, H., Lindgren, M., & Langel, Ü. (2007). Protein delivery by the cell-penetrating peptide YTA2. Bioconjugate Chemistry, 18, 170–174.PubMedPubMedCentralCrossRefGoogle Scholar
  324. Myrberg, H., Zhang, L., Mäe, M., & Langel, Ü. (2008). Design of a tumor-homing cell-penetrating peptide. Bioconjugate Chemistry, 19, 70–75.PubMedPubMedCentralCrossRefGoogle Scholar
  325. Mäe, M., Myrberg, H., Jiang, Y., Paves, H., Valkna, A., & Langel, Ü. (2005). Internalisation of cell-penetrating peptides into tobacco protoplasts. Biochimica et Biophysica Acta, 1669, 101–107.PubMedPubMedCentralCrossRefGoogle Scholar
  326. Mäe, M., Rautsi, O., Enbäck, J., Hällbrink, M., Rosenthal-Aizman, K., Lindgren, M., et al. (2012). Tumour targeting with rationally modified cell-penetrating peptides. International Journal of Peptide Research and Therapeutics, 18, 361–371.CrossRefGoogle Scholar
  327. Nain, V., Sahi, S., & Verma, A. (2010). CPP-ZFN: a potential DNA-targeting anti-malarial drug. Malaria Journal, 9, 258.PubMedPubMedCentralCrossRefGoogle Scholar
  328. Narla, A., Hurst, S. N., & Ebert, B. L. (2011). Ribosome defects in disorders of erythropoiesis. International Journal of Hematology, 93, 144–149.PubMedPubMedCentralCrossRefGoogle Scholar
  329. Nativo, P., Prior, I. A., & Brust, M. (2008). Uptake and intracellular fate of surface-modified gold nanoparticles. ACS Nano, 2, 1639–1644.PubMedPubMedCentralCrossRefGoogle Scholar
  330. Nekhotiaeva, N., Elmquist, A., Rajarao, G. K., Hällbrink, M., Langel, Ü., & Good, L. (2004). Cell entry and antimicrobial properties of eukaryotic cell-penetrating peptides. The FASEB Journal, 18, 394–396.PubMedPubMedCentralCrossRefGoogle Scholar
  331. Neo, S. H., Lew, Q. J., Koh, S. M., Zheng, L., Bi, X., & Chao, S. H. (2016). Use of a novel cytotoxic HEXIM1 peptide in the directed breast cancer therapy. Oncotarget, 7, 5483–5494.PubMedPubMedCentralCrossRefGoogle Scholar
  332. Neves-Coelho, S., Eleuterio, R. P., Enguita, F. J., Neves, V., & Castanho, M. (2017). A new noncanonical anionic peptide that translocates a cellular blood-brain barrier model. Molecules, 22.Google Scholar
  333. Nguyen, J., Xie, X., Neu, M., Dumitrascu, R., Reul, R., Sitterberg, J., et al. (2008). Effects of cell-penetrating peptides and pegylation on transfection efficiency of polyethylenimine in mouse lungs. The Journal of Gene Medicine, 10, 1236–1246.PubMedPubMedCentralCrossRefGoogle Scholar
  334. Nguyen, Q. T., Olson, E. S., Aguilera, T. A., Jiang, T., Scadeng, M., Ellies, L. G., et al. (2010). Surgery with molecular fluorescence imaging using activatable cell-penetrating peptides decreases residual cancer and improves survival. Proceedings of the National Academy of Sciences USA, 107, 4317–4322.CrossRefGoogle Scholar
  335. Nguyen, Q. T., & Tsien, R. Y. (2013). Fluorescence-guided surgery with live molecular navigation—A new cutting edge. Nature Reviews Cancer, 13, 653–662.PubMedPubMedCentralCrossRefGoogle Scholar
  336. Niazi, A. K., Mileshina, D., Cosset, A., Val, R., Weber-Lotfi, F., & Dietrich, A. (2013). Targeting nucleic acids into mitochondria: Progress and prospects. Mitochondrion, 13, 548–558.PubMedCrossRefGoogle Scholar
  337. Nielsen, E. J., Kamei, N., & Takeda-Morishita, M. (2015). Safety of the cell-penetrating peptide penetratin as an oral absorption enhancer. Biological and Pharmaceutical Bulletin, 38, 144–146.PubMedCrossRefGoogle Scholar
  338. Nielsen, E. J., Yoshida, S., Kamei, N., Iwamae, R., Khafagy el, S., Olsen, J., et al. (2014). In vivo proof of concept of oral insulin delivery based on a co-administration strategy with the cell-penetrating peptide penetratin. Journal of Controlled Release, 189, 19–24.PubMedCrossRefGoogle Scholar
  339. Niu, J., Chu, Y., Huang, Y. F., Chong, Y. S., Jiang, Z. H., Mao, Z. W., et al. (2017). Transdermal gene delivery by functional peptide-conjugated cationic gold nanoparticle reverses the progression and metastasis of cutaneous melanoma. ACS Applied Materials & Interfaces, 9, 9388–9401.CrossRefGoogle Scholar
  340. Niu, Z., Samaridou, E., Jaumain, E., Coene, J., Ullio, G., Shrestha, N., et al. (2018). PEG-PGA enveloped octaarginine-peptide nanocomplexes: An oral peptide delivery strategy. Journal of controlled release, 276, 125–139.PubMedCrossRefGoogle Scholar
  341. Nori, A., & Kopecek, J. (2005). Intracellular targeting of polymer-bound drugs for cancer chemotherapy. Advanced Drug Delivery Reviews, 57, 609–636.PubMedCrossRefGoogle Scholar
  342. Numata, K., Horii, Y., Oikawa, K., Miyagi, Y., Demura, T., & Ohtani, M. (2018). Library screening of cell-penetrating peptide for BY-2 cells, leaves of Arabidopsis, tobacco, tomato, poplar, and rice callus. Scientific Reports, 8, 10966.PubMedPubMedCentralCrossRefGoogle Scholar
  343. Numata, K., Ohtani, M., Yoshizumi, T., Demura, T., & Kodama, Y. (2014). Local gene silencing in plants via synthetic dsRNA and carrier peptide. Plant Biotechnology Journal, 12, 1027–1034.PubMedCrossRefGoogle Scholar
  344. Oller-Salvia, B., Sanchez-Navarro, M., Giralt, E., & Teixido, M. (2016). Blood-brain barrier shuttle peptides: An emerging paradigm for brain delivery. Chemical Society Reviews, 45, 4690–4707.PubMedCrossRefGoogle Scholar
  345. Oller-Salvia, B., Teixido, M., & Giralt, E. (2013). From venoms to BBB shuttles: Synthesis and blood-brain barrier transport assessment of apamin and a nontoxic analog. Biopolymers, 100, 675–686.PubMedCrossRefGoogle Scholar
  346. Olson, E. S., Aguilera, T. A., Jiang, T., Ellies, L. G., Nguyen, Q. T., Wong, E. H., et al. (2009). In vivo characterization of activatable cell penetrating peptides for targeting protease activity in cancer. Integrative Biology (Camb), 1, 382–393.PubMedCentralCrossRefPubMedGoogle Scholar
  347. Olson, E. S., Jiang, T., Aguilera, T. A., Nguyen, Q. T., Ellies, L. G., Scadeng, M., et al. (2010). Activatable cell penetrating peptides linked to nanoparticles as dual probes for in vivo fluorescence and MR imaging of proteases. Proceedings of the National Academy of Sciences USA, 107, 4311–4316.CrossRefGoogle Scholar
  348. Olson, E. S., Whitney, M. A., Friedman, B., Aguilera, T. A., Crisp, J. L., Baik, F. M., et al. (2012). In vivo fluorescence imaging of atherosclerotic plaques with activatable cell-penetrating peptides targeting thrombin activity. Integrative Biology (Camb), 4, 595–605.PubMedCentralCrossRefPubMedGoogle Scholar
  349. Orange, J. S., & May, M. J. (2008). Cell penetrating peptide inhibitors of nuclear factor-kappa B. Cellular and Molecular Life Sciences, 65, 3564–3591.PubMedPubMedCentralCrossRefGoogle Scholar
  350. Orihuela, C. J., Mahdavi, J., Thornton, J., Mann, B., Wooldridge, K. G., Abouseada, N., et al. (2009). Laminin receptor initiates bacterial contact with the blood brain barrier in experimental meningitis models. The Journal of Clinical Investigation, 119, 1638–1646.PubMedPubMedCentralCrossRefGoogle Scholar
  351. Osman, G., Rodriguez, J., Chan, S. Y., Chisholm, J., Duncan, G., Kim, N., et al. (2018). PEGylated enhanced cell penetrating peptide nanoparticles for lung gene therapy. Journal of Controlled Release, 285, 35–45.PubMedCrossRefGoogle Scholar
  352. Palm, C., Netzereab, S., & Hallbrink, M. (2006). Quantitatively determined uptake of cell-penetrating peptides in non-mammalian cells with an evaluation of degradation and antimicrobial effects. Peptides, 27, 1710–1716.CrossRefGoogle Scholar
  353. Pan, W., & Kastin, A. J. (2016). The blood-brain barrier: regulatory roles in wakefulness and sleep. Neuroscientist, 11, 1073858416639005.Google Scholar
  354. Pan, W., Kastin, A. J., Zankel, T. C., van Kerkhof, P., Terasaki, T., & Bu, G. (2004). Efficient transfer of receptor-associated protein (RAP) across the blood-brain barrier. Journal of Cell Science, 117, 5071–5078.PubMedCrossRefGoogle Scholar
  355. Pan, Z. Z., Wang, H. Y., Zhang, M., Lin, T. T., Zhang, W. Y., Zhao, P. F., et al. (2016). Nuclear-targeting TAT-PEG-Asp8-doxorubicin polymeric nanoassembly to overcome drug-resistant colon cancer. Acta Pharmacologica Sinica, 37, 1110–1120.PubMedPubMedCentralCrossRefGoogle Scholar
  356. Pardridge, W. M. (1986). Receptor-mediated peptide transport through the blood-brain barrier. Endocrine Reviews, 7, 314–330.PubMedCrossRefGoogle Scholar
  357. Pardridge, W. M. (1994). New approaches to drug delivery through the blood-brain barrier. Trends in Biotechnology, 12, 239–245.PubMedCrossRefGoogle Scholar
  358. Pardridge, W. M. (2001). Crossing the blood-brain barrier: Are we getting it right? Drug Discovery Today, 6, 1–2.PubMedCrossRefGoogle Scholar
  359. Pardridge, W. M. (2005). The blood-brain barrier: bottleneck in brain drug development. NeuroRx, 2, 3–14.PubMedPubMedCentralCrossRefGoogle Scholar
  360. Pardridge, W. M. (2006). Molecular Trojan horses for blood-brain barrier drug delivery. Discovery Medicine, 6, 139–143.PubMedGoogle Scholar
  361. Pardridge, W. M. (2007). Blood-brain barrier delivery. Drug Discovery Today, 12, 54–61.PubMedCrossRefGoogle Scholar
  362. Pardridge, W. M. (2010). Biologic TNFalpha-inhibitors that cross the human blood-brain barrier. Bioengineered Bugs, 1, 231–234.PubMedPubMedCentralCrossRefGoogle Scholar
  363. Pardridge, W. M. (2012). Drug transport across the blood-brain barrier. Journal of Cerebral Blood Flow & Metabolism, 32, 1959–1972.CrossRefGoogle Scholar
  364. Pardridge, W. M., Kumagai, A. K., & Eisenberg, J. B. (1987). Chimeric peptides as a vehicle for peptide pharmaceutical delivery through the blood-brain barrier. Biochemical and Biophysical Research Communications, 146, 307–313.PubMedCrossRefGoogle Scholar
  365. Parenteau, J., Klinck, R., Good, L., Langel, Ü., Wellinger, R. J., & Elela, S. A. (2005). Free uptake of cell-penetrating peptides by fission yeast. FEBS Letters, 579, 4873–4878.CrossRefGoogle Scholar
  366. Park, D., Lee, J. Y., Cho, H. K., Hong, W. J., Kim, J., Seo, H., et al. (2018a). Cell-penetrating peptide-patchy deformable polymeric nanovehicles with enhanced cellular uptake and transdermal delivery. Biomacromolecules.Google Scholar
  367. Park, J., Han, J. H., Myung, S. H., Seo, Y. W., & Kim, T. H. (2018b). MTD-like motif of a BH3-only protein, BNIP1, induces necrosis accompanied by an intracellular calcium spike. Biochemical and Biophysical Research Communications, 495, 1661–1667.PubMedCrossRefGoogle Scholar
  368. Patel, M. M., & Patel, B. M. (2017). Crossing the blood-brain barrier: Recent advances in drug delivery to the brain. CNS Drugs, 31, 109–133.CrossRefGoogle Scholar
  369. Patel, R. R., Sundin, G. W., Yang, C. H., Wang, J., Huntley, R. B., Yuan, X., et al. (2017). Exploration of using antisense Peptide Nucleic Acid (PNA)-cell Penetrating Peptide (CPP) as a novel bactericide against fire blight pathogen Erwinia amylovora. Frontiers in Microbiology, 8, 687.PubMedPubMedCentralGoogle Scholar
  370. Patra, S., Roy, E., Madhuri, R., & Sharma, P. K. (2016). The next generation cell-penetrating peptide and carbon dot conjugated nano-liposome for transdermal delivery of curcumin. Biomaterials Science, 4, 418–429.PubMedCrossRefGoogle Scholar
  371. Peng, J., Rao, Y., Yang, X., Jia, J., Wu, Y., Lu, J., et al. (2017). Targeting neuronal nitric oxide synthase by a cell penetrating peptide Tat-LK15/siRNA bioconjugate. Neuroscience Letters, 650, 153–160.PubMedPubMedCentralCrossRefGoogle Scholar
  372. Pepper, J. T., Maheshwari, P., & Eudes, F. (2017a). Adsorption of cell-penetrating peptide Tat2 and polycation luviquat FC-370 to triticale microspore exine. Colloids and Surfaces B: Biointerfaces, 157, 207–214.PubMedCrossRefGoogle Scholar
  373. Pepper, J. T., Maheshwari, P., Ziemienowicz, A., Hazendonk, P., Kovalchuk, I., & Eudes, F. (2017b). Tetrabutylphosphonium bromide reduces size and polydispersity index of Tat2:siRNA nano-complexes for triticale RNAi. Frontiers in Molecular Biosciences, 4, 30.PubMedPubMedCentralCrossRefGoogle Scholar
  374. Perera, Y., Costales, H. C., Diaz, Y., Reyes, O., Farina, H. G., Mendez, L., et al. (2012). Sensitivity of tumor cells towards CIGB-300 anticancer peptide relies on its nucleolar localization. Journal of Peptide Science, 18, 215–223.PubMedCrossRefGoogle Scholar
  375. Pero, S. C., Shukla, G. S., Cookson, M. M., Flemer, S., Jr., & Krag, D. N. (2007). Combination treatment with Grb7 peptide and Doxorubicin or Trastuzumab (Herceptin) results in cooperative cell growth inhibition in breast cancer cells. British Journal of Cancer, 96, 1520–1525.Google Scholar
  376. Petrescu, A. D., Vespa, A., Huang, H., McIntosh, A. L., Schroeder, F., & Kier, A. B. (2009). Fluorescent sterols monitor cell penetrating peptide Pep-1 mediated uptake and intracellular targeting of cargo protein in living cells. Biochimica et Biophysica Acta (BBA)-Biomembranes, 1788, 425–441.CrossRefGoogle Scholar
  377. Petrilli, R., Eloy, J. O., Praca, F. S., del Ciampo, J. O., Fantini, M. A., Fonseca, M. J., et al. (2016). Liquid crystalline nanodispersions functionalized with cell-penetrating peptides for topical delivery of short-interfering RNAs: A proposal for silencing a pro-inflammatory cytokine in cutaneous diseases. Journal of Biomedical Nanotechnology, 12, 1063–1075.PubMedCrossRefGoogle Scholar
  378. Poduslo, J. F., & Curran, G. L. (1994). Glycation increases the permeability of proteins across the blood-nerve and blood-brain barriers. Molecular Brain Research, 23, 157–162.PubMedCrossRefGoogle Scholar
  379. Ponnappan, N., Budagavi, D. P., & Chugh, A. (2017). CyLoP-1: Membrane-active peptide with cell-penetrating and antimicrobial properties. Biochimica et Biophysica Acta (BBA)-Biomembranes, 1859, 167–176.CrossRefGoogle Scholar
  380. Pooga, M., Hällbrink, M., Zorko, M., & Langel, Ü. (1998). Cell penetration by transportan. The FASEB Journal, 12, 67–77.PubMedPubMedCentralCrossRefGoogle Scholar
  381. Pouniotis, D., Tang, C. K., Apostolopoulos, V., & Pietersz, G. (2016). Vaccine delivery by penetratin: Mechanism of antigen presentation by dendritic cells. Immunologic Research, 64, 887–900.PubMedCrossRefGoogle Scholar
  382. Puckett, C. A., & Barton, J. K. (2010). Targeting a ruthenium complex to the nucleus with short peptides. Bioorganic & Medicinal Chemistry, 18, 3564–3569.CrossRefGoogle Scholar
  383. Puria, R., Sahi, S., & Nain, V. (2012). HER2+ breast cancer therapy: By CPP-ZFN mediated targeting of mTOR? Technology in Cancer Research & Treatment, 11, 175–180.CrossRefGoogle Scholar
  384. Qi, X., Droste, T., & Kao, C. C. (2011). Cell-penetrating peptides derived from viral capsid proteins. Molecular Plant-Microbe Interactions, 24, 25–36.PubMedCrossRefGoogle Scholar
  385. Qian, Z. M., Li, H., Sun, H., & Ho, K. (2002). Targeted drug delivery via the transferrin receptor-mediated endocytosis pathway. Pharmacological Reviews, 54, 561–587.PubMedCrossRefGoogle Scholar
  386. Qifan, W., Fen, N., Ying, X., Xinwei, F., Jun, D., & Ge, Z. (2016). iRGD-targeted delivery of a pro-apoptotic peptide activated by cathepsin B inhibits tumor growth and metastasis in mice. Tumor Biology, 11, 11.Google Scholar
  387. Raagel, H., Lust, M., Uri, A., & Pooga, M. (2008). Adenosine-oligoarginine conjugate, a novel bisubstrate inhibitor, effectively dissociates the actin cytoskeleton. The FEBS Journal, 275, 3608–3624.PubMedCrossRefGoogle Scholar
  388. Radis-Baptista, G., de la Torre, B. G., & Andreu, D. (2008). A novel cell-penetrating peptide sequence derived by structural minimization of a snake toxin exhibits preferential nucleolar localization. Journal of Medicinal Chemistry, 51, 7041–7044.PubMedCrossRefGoogle Scholar
  389. Radis-Baptista, G., de la Torre, B. G., & Andreu, D. (2012). Insights into the uptake mechanism of NrTP, a cell-penetrating peptide preferentially targeting the nucleolus of tumour cells. Chemical Biology & Drug Design, 79, 907–915.CrossRefGoogle Scholar
  390. Radis-Baptista, G., & Kerkis, I. (2011). Crotamine, a small basic polypeptide myotoxin from rattlesnake venom with cell-penetrating properties. Current Pharmaceutical Design, 17, 4351–4361.PubMedCrossRefGoogle Scholar
  391. Ran, R., Wang, H., Liu, Y., Hui, Y., Sun, Q., & Seth, A., et al. (2018). Microfluidic self-assembly of a combinatorial library of single- and dual-ligand liposomes for in vitro and in vivo tumor targeting. European Journal of Pharmaceutics and Biopharmaceutics.Google Scholar
  392. Ran, Y., Liang, Z., & Gao, C. (2017). Current and future editing reagent delivery systems for plant genome editing. Science China Life Sciences, 60, 490–505.PubMedCrossRefGoogle Scholar
  393. Rao, K. S., Reddy, M. K., Horning, J. L., & Labhasetwar, V. (2008). TAT-conjugated nanoparticles for the CNS delivery of anti-HIV drugs. Biomaterials, 29, 4429–4438.PubMedPubMedCentralCrossRefGoogle Scholar
  394. Rassu, G., Soddu, E., Posadino, A. M., Pintus, G., Sarmento, B., Giunchedi, P., et al. (2017). Nose-to-brain delivery of BACE1 siRNA loaded in solid lipid nanoparticles for Alzheimer’s therapy. Colloids and Surfaces B: Biointerfaces, 152, 296–301.CrossRefGoogle Scholar
  395. Regberg, J., Vasconcelos, L., Madani, F., Langel, Ü., & Hällbrink, M. (2016). pH-responsive PepFect cell-penetrating peptides. International Journal of Pharmaceutics, 501, 32–38.PubMedPubMedCentralCrossRefGoogle Scholar
  396. Ren, J., Shen, S., Wang, D., Xi, Z., Guo, L., Pang, Z., et al. (2012a). The targeted delivery of anticancer drugs to brain glioma by PEGylated oxidized multi-walled carbon nanotubes modified with angiopep-2. Biomaterials, 33, 3324–3333.PubMedCrossRefGoogle Scholar
  397. Ren, Y., Cheung, H. W., Von Maltzhan, G., Agrawal, A., Cowley, G. S., Weir, B. A., et al. (2012b). Targeted tumor-penetrating siRNA nanocomplexes for credentialing the ovarian cancer oncogene ID4. Science Translational Medicine, 4, 147ra112.PubMedPubMedCentralCrossRefGoogle Scholar
  398. Resina, S., Abes, S., Turner, J. J., Prevot, P., Travo, A., Clair, P., et al. (2007). Lipoplex and peptide-based strategies for the delivery of steric-block oligonucleotides. International Journal of Pharmaceutics, 344, 96–102.PubMedCrossRefGoogle Scholar
  399. Rhee, M., & Davis, P. (2006). Mechanism of uptake of C105Y, a novel cell-penetrating peptide. Journal of Biological Chemistry, 281, 1233–1240.CrossRefGoogle Scholar
  400. Richardson, A., Muir, L., Mousdell, S., Sexton, D., Jones, S., Howl, J., et al. (2018). Modulation of mitochondrial activity in HaCaT keratinocytes by the cell penetrating peptide Z-Gly-RGD(DPhe)-mitoparan. BMC Research Notes, 11, 82.PubMedPubMedCentralCrossRefGoogle Scholar
  401. Rip, J., Schenk, G. J., & de Boer, A. G. (2009). Differential receptor-mediated drug targeting to the diseased brain. Expert Opinion on Drug Delivery, 6, 227–237.PubMedCrossRefGoogle Scholar
  402. Robbins, J., Dilworth, S. M., Laskey, R. A., & Dingwall, C. (1991). Two interdependent basic domains in nucleoplasmin nuclear targeting sequence: identification of a class of bipartite nuclear targeting sequence. Cell, 64, 615–623.PubMedCrossRefGoogle Scholar
  403. Rodrigues, M., Andreu, D., & Santos, N. C. (2015). Uptake and cellular distribution of nucleolar targeting peptides (NrTPs) in different cell types. Biopolymers, 104, 101–109.PubMedPubMedCentralCrossRefGoogle Scholar
  404. Rodriguez-Moreno, L., Song, Y., & Thomma, B. P. (2017). Transfer and engineering of immune receptors to improve recognition capacities in crops. Current Opinion in Plant Biology, 38, 42–49.PubMedCrossRefGoogle Scholar
  405. Rogers, F. A., Manoharan, M., Rabinovitch, P., Ward, D. C., & Glazer, P. M. (2004). Peptide conjugates for chromosomal gene targeting by triplex-forming oligonucleotides. Nucleic Acids Research, 32, 6595–6604.PubMedPubMedCentralCrossRefGoogle Scholar
  406. Rosenbluh, J., Singh, S. K., Gafni, Y., Graessmann, A., & Loyter, A. (2004). Non-endocytic penetration of core histones into petunia protoplasts and cultured cells: A novel mechanism for the introduction of macromolecules into plant cells. Biochimica et Biophysica Acta (BBA)-Biomembranes, 1664, 230–240.CrossRefGoogle Scholar
  407. Ross, M. F., Filipovska, A., Smith, R. A., Gait, M. J., & Murphy, M. P. (2004). Cell-penetrating peptides do not cross mitochondrial membranes even when conjugated to a lipophilic cation: Evidence against direct passage through phospholipid bilayers. Biochemical Journal, 383, 457–468.PubMedPubMedCentralCrossRefGoogle Scholar
  408. Rothbard, J. B., Garlington, S., Lin, Q., Kirschberg, T., Kreider, E., McGrane, P. L., et al. (2000). Conjugation of arginine oligomers to cyclosporin A facilitates topical delivery and inhibition of inflammation. Nature Medicine, 6, 1253–1257.PubMedPubMedCentralCrossRefGoogle Scholar
  409. Roy, R. N., Lomakin, I. B., Gagnon, M. G., & Steitz, T. A. (2015). The mechanism of inhibition of protein synthesis by the proline-rich peptide oncocin. Nature Structural & Molecular Biology, 22, 466–469.CrossRefGoogle Scholar
  410. Ruan, S., Yuan, M., Zhang, L., Hu, G., Chen, J., Cun, X., et al. (2015). Tumor microenvironment sensitive doxorubicin delivery and release to glioma using angiopep-2 decorated gold nanoparticles. Biomaterials, 37, 425–435.PubMedCrossRefGoogle Scholar
  411. Ruge, C. A., Kirch, J., & Lehr, C. M. (2013). Pulmonary drug delivery: From generating aerosols to overcoming biological barriers-therapeutic possibilities and technological challenges. The Lancet Respiratory Medicine, 1, 402–413.PubMedCrossRefGoogle Scholar
  412. Ruoslahti, E. (2017). Tumor penetrating peptides for improved drug delivery. Advanced Drug Delivery Reviews, 111, 3–12.CrossRefGoogle Scholar
  413. Räägel, H., Säälik, P., Langel, Ü., & Pooga, M. (2011). Mapping of protein transduction pathways with fluorescent microscopy. Methods Mol Biol, 683, 165–179.PubMedCrossRefGoogle Scholar
  414. Sakhrani, N. M., & Padh, H. (2013). Organelle targeting: third level of drug targeting. Drug Design, Development and Therapy, 7, 585–599.PubMedPubMedCentralGoogle Scholar
  415. Sakurai, Y., Mizumura, W., Murata, M., Hada, T., Yamamoto, S., Ito, K., et al. (2017). Efficient siRNA delivery by lipid nanoparticles modified with a non-standard macrocyclic peptide for EpCAM-targeting. Molecular Pharmaceutics, 8.Google Scholar
  416. Sallevelt, S. C., De Die-Smulders, C. E., Hendrickx, A. T., Hellebrekers, D. M., de Coo, I. F., Alston, C. L., et al. (2017). De novo mtDNA point mutations are common and have a low recurrence risk. Journal of Medical Genetics, 54, 73–83.PubMedCrossRefGoogle Scholar
  417. Samuel, J. P., Samboju, N. C., Yau, K. Y., Lin, G., Webb, S. R., & Burroughs, F. (2013). Quantum dot carrier peptide conjugates suitable for imaging and delivery applications in plants. Google Patents.Google Scholar
  418. Santra, S., Yang, H., Stanley, J. T., Holloway, P. H., Moudgil, B. M., Walter, G., et al. (2005). Rapid and effective labeling of brain tissue using TAT-conjugated CdS:Mn/ZnS quantum dots. Chemical Communications (Camb), 3144–3146.Google Scholar
  419. Sato, Y., Nakamura, T., Yamada, Y., Akita, H., & Harashima, H. (2014). Multifunctional enveloped nanodevices (MENDs). Advances in Genetics, 88, 139–204.PubMedCrossRefGoogle Scholar
  420. Sawahel, W. A. (2001). Stable genetic transformation of cotton plants using polybrene-spermidine treatment. Plant Molecular Biology Reporter, 19, 377.CrossRefGoogle Scholar
  421. Savariar, E. N., Felsen, C. N., Nashi, N., Jiang, T., Ellies, L. G., Steinbach, P., et al. (2013). Real-time in vivo molecular detection of primary tumors and metastases with ratiometric activatable cell-penetrating peptides. Cancer Research, 73, 855–864.PubMedPubMedCentralCrossRefGoogle Scholar
  422. Schulz, R., Yamamoto, K., Klossek, A., Flesch, R., Honzke, S., Rancan, F., et al. (2017). Data-based modeling of drug penetration relates human skin barrier function to the interplay of diffusivity and free-energy profiles. Proceedings of the National Academy of Sciences USA, 114, 3631–3636.CrossRefGoogle Scholar
  423. Schwarze, S. R., Ho, A., Vocero-Akbani, A., & Dowdy, S. F. (1999). In vivo protein transduction: Delivery of a biologically active protein into the mouse. Science, 285, 1569–1572.CrossRefGoogle Scholar
  424. Selmin, F., Magri, G., Gennari, C. G., Marchiano, S., Ferri, N., & Pellegrino, S. (2017). Development of poly(lactide-co-glycolide) nanoparticles functionalized with a mitochondria penetrating peptide. Journal of Peptide Science, 23, 182–188.PubMedCrossRefGoogle Scholar
  425. Shabanpoor, F., Hammond, S. M., Abendroth, F., Hazell, G., Wood, M. J. A., & Gait, M. J. (2017). Identification of a peptide for systemic brain delivery of a morpholino oligonucleotide in mouse models of spinal muscular atrophy. Nucleic Acid Therapeutics, 27, 130–143.PubMedPubMedCentralCrossRefGoogle Scholar
  426. Shamay, Y., Shpirt, L., Ashkenasy, G., & David, A. (2014). Complexation of cell-penetrating peptide-polymer conjugates with polyanions controls cells uptake of HPMA copolymers and anti-tumor activity. Pharmaceutical Research, 31, 768–779.PubMedCrossRefGoogle Scholar
  427. Sharma, G., Modgil, A., Zhong, T., Sun, C., & Singh, J. (2014). Influence of short-chain cell-penetrating peptides on transport of doxorubicin encapsulating receptor-targeted liposomes across brain endothelial barrier. Pharmaceutical Research, 31, 1194–1209.PubMedCrossRefGoogle Scholar
  428. Shearer, A. M., Rana, R., Austin, K., Baleja, J. D., Nguyen, N., Bohm, A., et al. (2016). Targeting liver fibrosis with a cell-penetrating Protease-activated Receptor-2 (PAR2) pepducin. Journal of Biological Chemistry, 291, 23188–23198.PubMedPubMedCentralCrossRefGoogle Scholar
  429. Shenoy, N., Kessel, R., Bhagat, T. D., Bhattacharyya, S., Yu, Y., McMahon, C., et al. (2012). Alterations in the ribosomal machinery in cancer and hematologic disorders. Journal of Hematology & Oncology, 5, 1756–8722.CrossRefGoogle Scholar
  430. Shi, K., Long, Y., Xu, C., Wang, Y., Qiu, Y., Yu, Q., et al. (2015). Liposomes combined an integrin alphabeta-specific vector with pH-responsible cell-penetrating property for highly effective antiglioma therapy through the blood-brain barrier. ACS Applied Materials & Interfaces.Google Scholar
  431. Shi, N. Q., Gao, W., Xiang, B., & Qi, X. R. (2012). Enhancing cellular uptake of activable cell-penetrating peptide-doxorubicin conjugate by enzymatic cleavage. International Journal of Nanomedicine, 7, 1613–1621.PubMedPubMedCentralGoogle Scholar
  432. Shi, N. Q., Qi, X. R., Xiang, B., & Zhang, Y. (2014). A survey on “Trojan Horse” peptides: Opportunities, issues and controlled entry to “Troy”. Journal of Controlled Release, 194, 53–70.PubMedCrossRefGoogle Scholar
  433. Shim, Y.-S., Eudes, F., & Kovalchuk, I. (2013). dsDNA and protein co-delivery in triticale microspores. Vitro Cellular & Developmental Biology - Plant, 49, 156–165.CrossRefGoogle Scholar
  434. Shin, M. C., Zhang, J., Min, K. A., Lee, K., Moon, C., Balthasar, J. P., et al. (2014a). Combination of antibody targeting and PTD-mediated intracellular toxin delivery for colorectal cancer therapy. Journal of Controlled Release, 194, 197–210.PubMedPubMedCentralCrossRefGoogle Scholar
  435. Shin, T. H., Sung, E. S., Kim, Y. J., Kim, K. S., Kim, S. H., Kim, S. K., et al. (2014b). Enhancement of the tumor penetration of monoclonal antibody by fusion of a neuropilin-targeting peptide improves the antitumor efficacy. Molecular Cancer Therapeutics, 13, 651–661.PubMedPubMedCentralCrossRefGoogle Scholar
  436. Shteinfer-Kuzmine, A., Arif, T., Krelin, Y., Tripathi, S. S., Paul, A., & Shoshan-Barmatz, V. (2017). Mitochondrial VDAC1-based peptides: Attacking oncogenic properties in glioblastoma. Oncotarget, 8, 31329–31346.PubMedPubMedCentralCrossRefGoogle Scholar
  437. Sibrian-Vazquez, M., Jensen, T. J., & Vicente, M. G. (2008). Synthesis, characterization, and metabolic stability of porphyrin-peptide conjugates bearing bifunctional signaling sequences. Journal of Medicinal Chemistry, 51, 2915–2923.PubMedCrossRefGoogle Scholar
  438. Simon, M. J., Kang, W. H., Gao, S., Banta, S., & Morrison, B., III. (2011). TAT is not capable of transcellular delivery across an intact endothelial monolayer in vitro. Annals of Biomedical Engineering, 39, 394–401.Google Scholar
  439. Skarlatos, S., Yoshikawa, T., & Pardridge, W. M. (1995). Transport of [125I]transferrin through the rat blood-brain barrier. Brain Research, 683, 164–171.PubMedCrossRefGoogle Scholar
  440. Skrlj, N., & Dolinar, M. (2014). New engineered antibodies against prions. Bioengineered, 5, 10–14.PubMedCrossRefGoogle Scholar
  441. Skrlj, N., Drevensek, G., Hudoklin, S., Romih, R., Curin Serbec, V., & Dolinar, M. (2013). Recombinant single-chain antibody with the Trojan peptide penetratin positioned in the linker region enables cargo transfer across the blood-brain barrier. Applied Biochemistry and Biotechnology, 169, 159–169.Google Scholar
  442. Smilansky, A., Dangoor, L., Nakdimon, I., Ben-Hail, D., Mizrachi, D., & Shoshan-Barmatz, V. (2015). The voltage-dependent anion channel 1 mediates amyloid beta toxicity and represents a potential target for alzheimer disease therapy. Journal of Biological Chemistry, 290, 30670–30683.PubMedPubMedCentralCrossRefGoogle Scholar
  443. Snyder, E. L., Meade, B. R., Saenz, C. C., & Dowdy, S. F. (2004). Treatment of terminal peritoneal carcinomatosis by a transducible p53-activating peptide. PLoS Biology, 2, 17.CrossRefGoogle Scholar
  444. Snyder, E. L., Saenz, C. C., Denicourt, C., Meade, B. R., Cui, X. S., Kaplan, I. M., et al. (2005). Enhanced targeting and killing of tumor cells expressing the CXC chemokine receptor 4 by transducible anticancer peptides. Cancer Research, 65, 10646–10650.PubMedPubMedCentralCrossRefGoogle Scholar
  445. Solomon, M., & Muro, S. (2017). Lysosomal enzyme replacement therapies: Historical development, clinical outcomes, and future perspectives. Advanced Drug Delivery Reviews, 11, 30060–30061.Google Scholar
  446. Song, H., Zhang, J., Wang, W., Huang, P., Zhang, Y., Liu, J., et al. (2015). Acid-responsive PEGylated doxorubicin prodrug nanoparticles for neuropilin-1 receptor-mediated targeted drug delivery. Colloids and Surfaces B: Biointerfaces, 136, 365–374.PubMedCrossRefGoogle Scholar
  447. Sosnowski, T. R. (2016). Selected engineering and physicochemical aspects of systemic drug delivery by inhalation. Current Pharmaceutical Design, 22, 2453–2462.PubMedCrossRefGoogle Scholar
  448. Sousa, F., Castro, P., Fonte, P., Kennedy, P. J., Neves-Petersen, M. T., & Sarmento, B. (2016). Nanoparticles for the delivery of therapeutic antibodies: Dogma or promising strategy? Expert Opinion on Drug Delivery, 29, 1–14.Google Scholar
  449. Spencer, B., Williams, S., Rockenstein, E., Valera, E., Xin, W., Mante, M., et al. (2016). Alpha-synuclein conformational antibodies fused to penetratin are effective in models of Lewy body disease. Annals of Clinical and Translational Neurology, 3, 588–606.PubMedPubMedCentralCrossRefGoogle Scholar
  450. Spencer, B. J., & Verma, I. M. (2007). Targeted delivery of proteins across the blood-brain barrier. Proceedings of the National Academy of Sciences USA, 104, 7594–7599.CrossRefGoogle Scholar
  451. Srimanee, A., Arvanitidou, M., Kim, K., Hallbrink, M., & Langel, U. (2018). Cell-penetrating peptides for siRNA delivery to glioblastomas. Peptides, 104, 62–69.PubMedPubMedCentralCrossRefGoogle Scholar
  452. Srimanee, A., Regberg, J., Hallbrink, M., Vajragupta, O., & Langel, U. (2016). Role of scavenger receptors in peptide-based delivery of plasmid DNA across a blood-brain barrier model. International Journal of Pharmaceutics, 500, 128–135.PubMedPubMedCentralCrossRefGoogle Scholar
  453. Srimanee, A., Regberg, J., Hällbrink, M., Kurrikoff, K., Veiman, K.-L., Vajragupta, O., et al. (2014). Peptide based delivery of oligonucleotides across blood-brain barrier model. Journal of Peptide Research and Therapeutics, 20, 169–178.CrossRefGoogle Scholar
  454. Stalmans, S., Bracke, N., Wynendaele, E., Gevaert, B., Peremans, K., Burvenich, C., et al. (2015). Cell-penetrating peptides selectively cross the blood-brain barrier in vivo. PLoS One, 10.PubMedPubMedCentralCrossRefGoogle Scholar
  455. Suda, K., Murakami, T., Gotoh, N., Fukuda, R., Hashida, Y., Hashida, M., et al. (2017). High-density lipoprotein mutant eye drops for the treatment of posterior eye diseases. Journal of Controlled Release, 266, 301–309.PubMedCrossRefGoogle Scholar
  456. Sugahara, K. N., Teesalu, T., Karmali, P. P., Kotamraju, V. R., Agemy, L., Greenwald, D. R., et al. (2010). Coadministration of a tumor-penetrating peptide enhances the efficacy of cancer drugs. Science, 328, 1031–1035.PubMedPubMedCentralCrossRefGoogle Scholar
  457. Suk, J. S., Kim, A. J., Trehan, K., Schneider, C. S., Cebotaru, L., Woodward, O. M., et al. (2014). Lung gene therapy with highly compacted DNA nanoparticles that overcome the mucus barrier. Journal of Controlled Release, 178, 8–17.PubMedPubMedCentralCrossRefGoogle Scholar
  458. Sumbria, R. K., Boado, R. J., & Pardridge, W. M. (2013). Combination stroke therapy in the mouse with blood-brain barrier penetrating IgG-GDNF and IgG-TNF decoy receptor fusion proteins. Brain Research, 24, 91–96.CrossRefGoogle Scholar
  459. Sun, L., Xie, S., Ji, X., Zhang, J., Wang, D., Lee, S. J., et al. (2018). MMP-2-responsive fluorescent nanoprobes for enhanced selectivity of tumor cell uptake and imaging. Biomaterials Science.Google Scholar
  460. Sun, Y., Xian, L., Xing, H., Yu, J., Yang, Z., Yang, T., et al. (2016). Factors influencing the nuclear targeting ability of nuclear localization signals. Journal of Drug Targeting, 24, 927–933.PubMedCrossRefGoogle Scholar
  461. Suresh, A., & Kim, Y. C. (2013). Translocation of cell penetrating peptides on Chlamydomonas reinhardtii. Biotechnology and Bioengineering, 110, 2795–2801.PubMedCrossRefGoogle Scholar
  462. Swiecicki, J. M., di Pisa, M., Lippi, F., Chwetzoff, S., Mansuy, C., Trugnan, G., et al. (2015). Unsaturated acyl chains dramatically enhanced cellular uptake by direct translocation of a minimalist oligo-arginine lipopeptide. Chemical Communications (Camb), 51, 14656–14659.CrossRefGoogle Scholar
  463. Szeto, H. H. (2006a). Cell-permeable, mitochondrial-targeted, peptide antioxidants. The AAPS Journal, 8, E277–E283.PubMedPubMedCentralCrossRefGoogle Scholar
  464. Szeto, H. H. (2006b). Mitochondria-targeted peptide antioxidants: Novel neuroprotective agents. The AAPS Journal, 8, E521–E531.PubMedPubMedCentralCrossRefGoogle Scholar
  465. Tacken, P. J., Joosten, B., Reddy, A., Wu, D., Eek, A., Laverman, P., et al. (2008). No advantage of cell-penetrating peptides over receptor-specific antibodies in targeting antigen to human dendritic cells for cross-presentation. The Journal of Immunology, 180, 7687–7696.PubMedCrossRefGoogle Scholar
  466. Takara, K., Hatakeyama, H., Kibria, G., Ohga, N., Hida, K., & Harashima, H. (2012). Size-controlled, dual-ligand modified liposomes that target the tumor vasculature show promise for use in drug-resistant cancer therapy. Journal of Controlled Release, 162, 225–232.PubMedCrossRefGoogle Scholar
  467. Taki, H., Kanazawa, T., Akiyama, F., Takashima, Y., & Okada, H. (2012). Intranasal delivery of camptothecin-loaded tat-modified nanomicells for treatment of intracranial brain tumors. Pharmaceuticals (Basel), 5, 1092–1102.CrossRefGoogle Scholar
  468. Talvensaari-Mattila, A., Paakko, P., & Turpeenniemi-Hujanen, T. (2003). Matrix metalloproteinase-2 (MMP-2) is associated with survival in breast carcinoma. British Journal of Cancer, 89, 1270–1275.PubMedPubMedCentralCrossRefGoogle Scholar
  469. Tan, M., Lan, K. H., Yao, J., Lu, C. H., Sun, M., Neal, C. L., et al. (2006). Selective inhibition of ErbB2-overexpressing breast cancer in vivo by a novel TAT-based ErbB2-targeting signal transducers and activators of transcription 3-blocking peptide. Cancer Research, 66, 3764–3772.CrossRefGoogle Scholar
  470. Tan, R. S., Naruchi, K., Amano, M., Hinou, H., & Nishimura, S. (2015). Rapid endolysosomal escape and controlled intracellular trafficking of cell surface mimetic quantum-dots-anchored peptides and glycopeptides. ACS Chemical Biology, 10, 2073–2086.PubMedCrossRefGoogle Scholar
  471. Tashima, T. (2018). Effective cancer therapy based on selective drug delivery into cells across their membrane using receptor-mediated endocytosis. Bioorganic & Medicinal Chemistry Letters.Google Scholar
  472. Taylor, B. N., Mehta, R. R., Yamada, T., Lekmine, F., Christov, K., Chakrabarty, A. M., et al. (2009). Noncationic peptides obtained from azurin preferentially enter cancer cells. Cancer Research, 69, 537–546.PubMedPubMedCentralCrossRefGoogle Scholar
  473. Thomas, F. C., Taskar, K., Rudraraju, V., Goda, S., Thorsheim, H. R., Gaasch, J. A., et al. (2009). Uptake of ANG1005, a novel paclitaxel derivative, through the blood-brain barrier into brain and experimental brain metastases of breast cancer. Pharmaceutical Research, 26, 2486–2494.PubMedPubMedCentralCrossRefGoogle Scholar
  474. Tkachenko, A. G., Xie, H., Coleman, D., Glomm, W., Ryan, J., Anderson, M. F., et al. (2003). Multifunctional gold nanoparticle-peptide complexes for nuclear targeting. Journal of the American Chemical Society, 125, 4700–4701.PubMedCrossRefGoogle Scholar
  475. Toba, M., Alzoubi, A., O’Neill, K., Abe, K., Urakami, T., Komatsu, M., et al. (2014). A novel vascular homing peptide strategy to selectively enhance pulmonary drug efficacy in pulmonary arterial hypertension. The American Journal of Pathology, 184, 369–375.PubMedPubMedCentralCrossRefGoogle Scholar
  476. Torchilin, V. P. (2006). Recent approaches to intracellular delivery of drugs and DNA and organelle targeting. Annu Rev Biomed Eng, 8, 343–375.PubMedCrossRefGoogle Scholar
  477. Tünnemann, G., Martin, R. M., Haupt, S., Patsch, C., Edenhofer, F., & Cardoso, M. C. (2006). Cargo-dependent mode of uptake and bioavailability of TAT-containing proteins and peptides in living cells. The FASEB Journal, 20, 1775–1784.PubMedPubMedCentralCrossRefGoogle Scholar
  478. Uchida, T., Kanazawa, T., Takashima, Y., & Okada, H. (2011). Development of an efficient transdermal delivery system of small interfering RNA using functional peptides, Tat and AT-1002. Chemical and Pharmaceutical Bulletin (Tokyo), 59, 196–201.CrossRefGoogle Scholar
  479. Urgard, E., Lorents, A., Klaas, M., Padari, K., Viil, J., Runnel, T., et al. (2016). Pre-administration of PepFect6-microRNA-146a nanocomplexes inhibits inflammatory responses in keratinocytes and in a mouse model of irritant contact dermatitis. Journal of Controlled Release, 235, 195–204.CrossRefGoogle Scholar
  480. Wada, S. I., Iwata, M., Ozaki, Y., Ozaki, T., Hayashi, J., & Urata, H. (2016). Design of cyclic RGD-conjugated Aib-containing amphipathic helical peptides for targeted delivery of small interfering RNA. Bioorganic & Medicinal Chemistry, 24, 4478–4485.CrossRefGoogle Scholar
  481. Wadia, J. S., Stan, R. V., & Dowdy, S. F. (2004). Transducible TAT-HA fusogenic peptide enhances escape of TAT-fusion proteins after lipid raft macropinocytosis. Nature Medicine, 10, 310–315.PubMedPubMedCentralCrossRefGoogle Scholar
  482. Wagner, S., Zensi, A., Wien, S. L., Tschickardt, S. E., Maier, W., Vogel, T., et al. (2012). Uptake mechanism of ApoE-modified nanoparticles on brain capillary endothelial cells as a blood-brain barrier model. PLoS One, 7, 1.Google Scholar
  483. Wagstaff, K. M., Glover, D. J., Tremethick, D. J., & Jans, D. A. (2007). Histone-mediated transduction as an efficient means for gene delivery. Molecular Therapy, 15, 721–731.PubMedCrossRefGoogle Scholar
  484. Wahlmuller, F. C., Yang, H., Furtmuller, M., & Geiger, M. (2017). Regulation of the extracellular SERPINA5 (Protein C Inhibitor) penetration through cellular membranes. Adv Exp Med Biol, 22.Google Scholar
  485. Wallbrecher, R., Chene, P., Ruetz, S., Stachyra, T., Vorherr, T., & Brock, R. (2017). A critical assessment of the synthesis and biological activity of p53/human double minute 2-stapled peptide inhibitors. British Journal of Pharmacology, 174, 2613–2622.PubMedPubMedCentralCrossRefGoogle Scholar
  486. Walther, R., Rautio, J., & Zelikin, A. N. (2017). Prodrugs in medicinal chemistry and enzyme prodrug therapies. Advanced Drug Delivery Reviews, 1, 30097-2.Google Scholar
  487. van Duijnhoven, S. M., Robillard, M. S., Nicolay, K., & Grull, H. (2011). Tumor targeting of MMP-2/9 activatable cell-penetrating imaging probes is caused by tumor-independent activation. Journal of Nuclear Medicine, 52, 279–286.CrossRefGoogle Scholar
  488. van Duijnhoven, S. M., Robillard, M. S., Nicolay, K., & Grull, H. (2015). In vivo biodistribution of radiolabeled MMP-2/9 activatable cell-penetrating peptide probes in tumor-bearing mice. Contrast Media & Molecular Imaging, 10, 59–66.CrossRefGoogle Scholar
  489. van Lith, S. A. M., Van Den Brand, D., Wallbrecher, R., Wubbeke, L., van Duijnhoven, S. M. J., Makinen, P. I., et al. (2017). The effect of subcellular localization on the efficiency of EGFR-targeted VHH photosensitizer conjugates. European Journal of Pharmaceutics and Biopharmaceutics.Google Scholar
  490. Wang, H. Y., Chen, J. X., Sun, Y. X., Deng, J. Z., Li, C., Zhang, X. Z., et al. (2011). Construction of cell penetrating peptide vectors with N-terminal stearylated nuclear localization signal for targeted delivery of DNA into the cell nuclei. Journal of Controlled Release, 155, 26–33.CrossRefGoogle Scholar
  491. Wang, L., Hao, Y., Li, H., Zhao, Y., Meng, D., Li, D., et al. (2015a). Co-delivery of doxorubicin and siRNA for glioma therapy by a brain targeting system: angiopep-2-modified poly(lactic-co-glycolic acid) nanoparticles. Journal of Drug Targeting, 1–15.Google Scholar
  492. Wang, S., Huttmann, G., Zhang, Z., Vogel, A., Birngruber, R., Tangutoori, S., et al. (2015b). Light-controlled delivery of monoclonal antibodies for targeted photoinactivation of Ki-67. Molecular Pharmaceutics, 12, 3272–3281.PubMedCrossRefGoogle Scholar
  493. Wang, Z. Y., Liu, J. Y., Yang, C. B., Malampati, S., Huang, Y. Y., Li, M. X., et al. (2017). Neuroprotective natural products for the treatment of Parkinson’s disease by targeting the autophagy-lysosome pathway: A systematic review. Phytotherapy Research, 31, 1119–1127.PubMedCrossRefGoogle Scholar
  494. Watkins, G. A., Jones, E. F., Scott Shell, M., Vanbrocklin, H. F., Pan, M. H., Hanrahan, S. M., et al. (2009). Development of an optimized activatable MMP-14 targeted SPECT imaging probe. Bioorganic & Medicinal Chemistry, 17, 653–659.CrossRefGoogle Scholar
  495. Watson, V. G., Drake, K. M., Peng, Y., & Napper, A. D. (2013). Development of a high-throughput screening-compatible assay for the discovery of inhibitors of the AF4-AF9 interaction using AlphaScreen technology. Assay and Drug Development Technologies, 11, 253–268.PubMedPubMedCentralCrossRefGoogle Scholar
  496. Vazquez, O., Blanco-Canosa, J. B., Vazquez, M. E., Martinez-Costas, J., Castedo, L., & Mascarenas, J. L. (2008). Efficient DNA binding and nuclear uptake by distamycin derivatives conjugated to octa-arginine sequences. Chembiochem, 9, 2822–2829.PubMedCrossRefGoogle Scholar
  497. Veiman, K. L., Kunnapuu, K., Lehto, T., Kiisholts, K., Pärn, K., Langel, Ü., et al. (2015). PEG shielded MMP sensitive CPPs for efficient and tumor specific gene delivery in vivo. Journal of Controlled Release, 209, 238–247.PubMedPubMedCentralCrossRefGoogle Scholar
  498. Veiman, K. L., Mäger, I., Ezzat, K., Margus, H., Lehto, T., Langel, K., et al. (2013). PepFect14 peptide vector for efficient gene delivery in cell cultures. Molecular Pharmaceutics, 10, 199–210.CrossRefGoogle Scholar
  499. Weinstain, R., Savariar, E. N., Felsen, C. N., & Tsien, R. Y. (2014). In vivo targeting of hydrogen peroxide by activatable cell-penetrating peptides. Journal of the American Chemical Society, 136, 874–877.PubMedPubMedCentralCrossRefGoogle Scholar
  500. Weisbart, R. H., Chan, G., Jordaan, G., Noble, P. W., Liu, Y., Glazer, P. M., et al. (2015). DNA-dependent targeting of cell nuclei by a lupus autoantibody. Scientific Reports, 5.Google Scholar
  501. Weissig, V., & Torchilin, V. P. (2001). Cationic bolasomes with delocalized charge centers as mitochondria-specific DNA delivery systems. Advanced Drug Delivery Reviews, 49, 127–149.PubMedCrossRefGoogle Scholar
  502. Welch, J. J., Swanekamp, R. J., King, C., Dean, D. A., & Nilsson, B. L. (2016). Functional delivery of siRNA by disulfide-constrained cyclic amphipathic peptides. ACS Medicinal Chemistry Letters, 7, 584–589.PubMedPubMedCentralCrossRefGoogle Scholar
  503. Venkatachalam, A., Wood, C., Hu, Q., & Alwayn, I. (2015). Delivery of Heme Oxygenase-1-Cell Penetrating Peptide (HO-1-CPP) into hepatocytes, Kupffer and Islet cells in in vitro and ex vivo models of cold ischemia. American Journal of Transplantation, 15.Google Scholar
  504. Verheij, M. M., Vendruscolo, L. F., Caffino, L., Giannotti, G., Cazorla, M., Fumagalli, F., et al. (2016). Systemic delivery of a brain-penetrant TrkB antagonist reduces cocaine self-administration and normalizes TrkB signaling in the nucleus accumbens and prefrontal cortex. Journal of Neuroscience, 36, 8149–8159.PubMedCrossRefGoogle Scholar
  505. Whitney, M., Crisp, J. L., Olson, E. S., Aguilera, T. A., Gross, L. A., Ellies, L. G., et al. (2010). Parallel in vivo and in vitro selection using phage display identifies protease-dependent tumor-targeting peptides. Journal of Biological Chemistry, 285, 22532–22541.PubMedPubMedCentralCrossRefGoogle Scholar
  506. Whitney, M., Savariar, E. N., Friedman, B., Levin, R. A., Crisp, J. L., Glasgow, H. L., et al. (2013). Ratiometric activatable cell-penetrating peptides provide rapid in vivo readout of thrombin activation. Angewandte Chemie International Edition, 52, 325–330.PubMedCrossRefGoogle Scholar
  507. Viht, K., Padari, K., Raidaru, G., Subbi, J., Tammiste, I., Pooga, M., et al. (2003). Liquid-phase synthesis of a pegylated adenosine-oligoarginine conjugate, cell-permeable inhibitor of cAMP-dependent protein kinase. Bioorganic & Medicinal Chemistry Letters, 13, 3035–3039.CrossRefGoogle Scholar
  508. Vij, M., Alam, S., Gupta, N., Gotherwal, V., Gautam, H., Ansari, K. M., et al. (2017). Non-invasive oil-based method to increase topical delivery of nucleic acids to skin. Molecular Therapy, 25, 1342–1352.PubMedPubMedCentralCrossRefGoogle Scholar
  509. Vij, M., Natarajan, P., Pattnaik, B. R., Alam, S., Gupta, N., Santhiya, D., et al. (2016a). Non-invasive topical delivery of plasmid DNA to the skin using a peptide carrier. Journal of Controlled Release, 222, 159–168.CrossRefGoogle Scholar
  510. Vij, M., Natarajan, P., Yadav, A. K., Patil, K. M., Pandey, T., Gupta, N., et al. (2016b). Efficient cellular entry of (r-x-r)-type carbamate-plasmid DNA complexes and its implication for noninvasive topical DNA delivery to skin. Molecular Pharmaceutics, 13, 1779–1790.PubMedPubMedCentralCrossRefGoogle Scholar
  511. Wlodkowic, D., Skommer, J., McGuinness, D., Hillier, C., & Darzynkiewicz, Z. (2009). ER-Golgi network–a future target for anti-cancer therapy. Leukemia Research, 33, 1440–1447.PubMedPubMedCentralCrossRefGoogle Scholar
  512. Woldetsadik, A. D., Vogel, M. C., Rabeh, W. M., & Magzoub, M. (2017). Hexokinase II-derived cell-penetrating peptide targets mitochondria and triggers apoptosis in cancer cells. The FASEB Journal, 9.Google Scholar
  513. Wonder, E., Simon-Gracia, L., Scodeller, P., Majzoub, R. N., Kotamraju, V. R., Ewert, K. K., et al. (2018). Competition of charge-mediated and specific binding by peptide-tagged cationic liposome-DNA nanoparticles in vitro and in vivo. Biomaterials, 166, 52–63.PubMedPubMedCentralCrossRefGoogle Scholar
  514. Wu, J., Han, H., Jin, Q., Li, Z., Li, H., & Ji, J. (2017). Design and proof of programmed 5-Aminolevulinic acid prodrug nanocarriers for targeted photodynamic cancer therapy. ACS Applied Materials & Interfaces, 9, 14596–14605.CrossRefGoogle Scholar
  515. Wu, J., Zheng, Y., Liu, M., Shan, W., Zhang, Z., & Huang, Y. (2018). Biomimetic viruslike and charge reversible nanoparticles to sequentially overcome mucus and epithelial barriers for oral insulin delivery. ACS Applied Materials & Interfaces, 10, 9916–9928.CrossRefGoogle Scholar
  516. Wyatt, L. C., Moshnikova, A., Crawford, T., Engelman, D. M., Andreev, O. A., & Reshetnyak, Y. K. (2018). Peptides of pHLIP family for targeted intracellular and extracellular delivery of cargo molecules to tumors. Proceedings of the National Academy of Sciences USA, 115, E2811–E2818.CrossRefGoogle Scholar
  517. Xia, H., Gao, X., Gu, G., Liu, Z., Hu, Q., Tu, Y., et al. (2012). Penetratin-functionalized PEG-PLA nanoparticles for brain drug delivery. International Journal of Pharmaceutics, 436, 840–850.PubMedCrossRefGoogle Scholar
  518. Xia, H., Gao, X., Gu, G., Liu, Z., Zeng, N., Hu, Q., et al. (2011). Low molecular weight protamine-functionalized nanoparticles for drug delivery to the brain after intranasal administration. Biomaterials, 32, 9888–9898.PubMedPubMedCentralCrossRefGoogle Scholar
  519. Xiang, B., Dong, D. W., Shi, N. Q., Gao, W., Yang, Z. Z., Cui, Y., et al. (2013). PSA-responsive and PSMA-mediated multifunctional liposomes for targeted therapy of prostate cancer. Biomaterials, 34, 6976–6991.PubMedCrossRefGoogle Scholar
  520. Xin, H., Sha, X., Jiang, X., Zhang, W., Chen, L., & Fang, X. (2012). Anti-glioblastoma efficacy and safety of paclitaxel-loading Angiopep-conjugated dual targeting PEG-PCL nanoparticles. Biomaterials, 33, 8167–8176.PubMedCrossRefGoogle Scholar
  521. Yaghini, E., Dondi, R., Tewari, K. M., Loizidou, M., Eggleston, I. M., & Macrobert, A. J. (2017). Endolysosomal targeting of a clinical chlorin photosensitiser for light-triggered delivery of nano-sized medicines. Scientific Reports, 7, 6059.PubMedPubMedCentralCrossRefGoogle Scholar
  522. Yamada, Y., Furukawa, R., & Harashima, H. (2016). A dual-ligand liposomal system composed of a cell-penetrating peptide and a mitochondrial RNA aptamer synergistically facilitates cellular uptake and mitochondrial targeting. Journal of Pharmaceutical Sciences, 4, 00402.Google Scholar
  523. Yamada, Y., Perez, S. M., Tabata, M., Abe, J., Yasuzaki, Y., & Harashima, H. (2015). Efficient and high-speed transduction of an antibody into living cells using a multifunctional nanocarrier system to control intracellular trafficking. Journal of Pharmaceutical Sciences, 104, 2845–2854.PubMedCrossRefGoogle Scholar
  524. Yamamoto, S., Kato, A., Sakurai, Y., Hada, T., & Harashima, H. (2017). Modality of tumor endothelial VEGFR2 silencing-mediated improvement in intratumoral distribution of lipid nanoparticles. Journal of Controlled Release, 251, 1–10.PubMedCrossRefGoogle Scholar
  525. Yameen, B., Choi, W. I., Vilos, C., Swami, A., Shi, J., & Farokhzad, O. C. (2014). Insight into nanoparticle cellular uptake and intracellular targeting. Journal of Controlled Release, 190, 485–499.PubMedPubMedCentralCrossRefGoogle Scholar
  526. Yan, H., Wang, J., Yi, P., Lei, H., Zhan, C., Xie, C., et al. (2011). Imaging brain tumor by dendrimer-based optical/paramagnetic nanoprobe across the blood-brain barrier. Chemical Communications, 47, 8130–8132.PubMedCrossRefGoogle Scholar
  527. Yanez, R. J. R., Lamprecht, R., Granadillo, M., Torrens, I., Arcalis, E., Stoger, E., et al. (2017a). LALF32-51 -E7, a HPV-16 therapeutic vaccine candidate, forms protein body-like structures when expressed in Nicotiana benthamiana leaves. Plant Biotechnology Journal.Google Scholar
  528. Yanez, R. J. R., Lamprecht, R., Granadillo, M., Weber, B., Torrens, I., Rybicki, E. P., et al. (2017b). Expression optimization of a cell membrane-penetrating human papillomavirus type 16 therapeutic vaccine candidate in Nicotiana benthamiana. PLoS One, 12, e0183177.PubMedPubMedCentralCrossRefGoogle Scholar
  529. Yang, J., Li, Q., Yang, X., Feng, Y., Ren, X., Shi, C., et al. (2016). Multitargeting gene delivery systems for enhancing the transfection of endothelial cells. Macromolecular Rapid Communications, 37, 1926–1931.PubMedPubMedCentralCrossRefGoogle Scholar
  530. Yang, Y., Xie, X., Cai, X., Wang, Z., Gong, W., Zhang, H., et al. (2015). A near-infrared two-photon-sensitive peptide-mediated liposomal delivery system. Colloids and Surfaces B: Biointerfaces, 128, 427–438.PubMedCrossRefGoogle Scholar
  531. Yang, Z. Z., Li, J. Q., Wang, Z. Z., Dong, D. W., & Qi, X. R. (2014). Tumor-targeting dual peptides-modified cationic liposomes for delivery of siRNA and docetaxel to gliomas. Biomaterials, 35, 5226–5239.PubMedCrossRefGoogle Scholar
  532. Ye, J., Shin, M. C., Liang, Q., He, H., & Yang, V. C. (2015). 15 years of ATTEMPTS: A macromolecular drug delivery system based on the CPP-mediated intracellular drug delivery and antibody targeting. Journal of Controlled Release, 205, 58–69.PubMedPubMedCentralCrossRefGoogle Scholar
  533. Yoneda, Y., Semba, T., Kaneda, Y., Noble, R. L., Matsuoka, Y., Kurihara, T., et al. (1992). A long synthetic peptide containing a nuclear localization signal and its flanking sequences of SV40 T-antigen directs the transport of IgM into the nucleus efficiently. Experimental Cell Research, 201, 313–320.PubMedPubMedCentralCrossRefGoogle Scholar
  534. Yoneda, Y., Steiniger, S. C., Capkova, K., Mee, J. M., Liu, Y., Kaufmann, G. F., et al. (2008). A cell-penetrating peptidic GRP78 ligand for tumor cell-specific prodrug therapy. Bioorganic & Medicinal Chemistry Letters, 18, 1632–1636.CrossRefGoogle Scholar
  535. Youn, P., Chen, Y., & Furgeson, D. Y. (2014). A myristoylated cell-penetrating peptide bearing a transferrin receptor-targeting sequence for neuro-targeted siRNA delivery. Molecular Pharmaceutics, 11, 486–495.PubMedPubMedCentralCrossRefGoogle Scholar
  536. Younis, A., Siddique, M. I., Kim, C. K., & Lim, K. B. (2014). RNA Interference (RNAi) induced gene silencing: A promising approach of hi-tech plant breeding. International Journal of Biological Sciences, 10, 1150–1158.PubMedPubMedCentralCrossRefGoogle Scholar
  537. Yu, Y. J., Zhang, Y., Kenrick, M., Hoyte, K., Luk, W., Lu, Y., et al. (2011). Boosting brain uptake of a therapeutic antibody by reducing its affinity for a transcytosis target. Science Translational Medicine, 3, 3002230.CrossRefGoogle Scholar
  538. Yuan, X., Lin, X., Manorek, G., & Howell, S. B. (2011). Challenges associated with the targeted delivery of gelonin to claudin-expressing cancer cells with the use of activatable cell penetrating peptides to enhance potency. BMC Cancer, 11, 1471–2407.Google Scholar
  539. Yurlova, L., Derks, M., Buchfellner, A., Hickson, I., Janssen, M., Morrison, D., et al. (2014). The fluorescent two-hybrid assay to screen for protein-protein interaction inhibitors in live cells: targeting the interaction of p53 with Mdm2 and Mdm4. Journal of Biomolecular Screening, 19, 516–525.PubMedCrossRefGoogle Scholar
  540. Zannikou, M., Bellou, S., Eliades, P., Hatzioannou, A., Mantzaris, M. D., Carayanniotis, G., et al. (2016). DNA-histone complexes as ligands amplify cell penetration and nuclear targeting of anti-DNA antibodies via energy-independent mechanisms. Immunology, 147, 73–81.PubMedCrossRefGoogle Scholar
  541. Zaro, J. L., Vekich, J. E., Tran, T., & Shen, W. C. (2009). Nuclear localization of cell-penetrating peptides is dependent on endocytosis rather than cytosolic delivery in CHO cells. Molecular Pharmaceutics, 6, 337–344.PubMedPubMedCentralCrossRefGoogle Scholar
  542. Zhan, C., Li, B., Hu, L., Wei, X., Feng, L., Fu, W., et al. (2011). Micelle-based brain-targeted drug delivery enabled by a nicotine acetylcholine receptor ligand. Angewandte Chemie International Edition, 50, 5482–5485.PubMedCrossRefGoogle Scholar
  543. Zhan, C., Yan, Z., Xie, C., & Lu, W. (2010). Loop 2 of Ophiophagus hannah toxin b binds with neuronal nicotinic acetylcholine receptors and enhances intracranial drug delivery. Molecular Pharmaceutics, 7, 1940–1947.PubMedCrossRefGoogle Scholar
  544. Zhang, Q., Tang, J., Fu, L., Ran, R., Liu, Y., Yuan, M., et al. (2013). A pH-responsive alpha-helical cell penetrating peptide-mediated liposomal delivery system. Biomaterials, 34, 7980–7993.PubMedCrossRefGoogle Scholar
  545. Zhang, T., Qu, H., Li, X., Zhao, B., Zhou, J., Li, Q., et al. (2010). Transmembrane delivery and biological effect of human growth hormone via a phage displayed peptide in vivo and in vitro. Journal of Pharmaceutical Science, 99, 4880–4891.CrossRefGoogle Scholar
  546. Zhao, B. Q., Guo, Y. R., Li, X. L., Zang, T., Qu, H. Y., Zhou, J. P., et al. (2011). Amelioration of dementia induced by Abeta 22-35 through rectal delivery of undecapeptide-hEGF to mouse brain. International Journal of Pharmaceutics, 405, 1–8.PubMedPubMedCentralCrossRefGoogle Scholar
  547. Zhao, B. X., Zhao, Y., Huang, Y., Luo, L. M., Song, P., Wang, X., et al. (2012). The efficiency of tumor-specific pH-responsive peptide-modified polymeric micelles containing paclitaxel. Biomaterials, 33, 2508–2520.PubMedCrossRefGoogle Scholar
  548. Zhao, K., Luo, G., Giannelli, S., & Szeto, H. H. (2005). Mitochondria-targeted peptide prevents mitochondrial depolarization and apoptosis induced by tert-butyl hydroperoxide in neuronal cell lines. Biochemical Pharmacology, 70, 1796–1806.PubMedPubMedCentralCrossRefGoogle Scholar
  549. Zhao, K., Luo, G., Zhao, G. M., Schiller, P. W., & Szeto, H. H. (2003). Transcellular transport of a highly polar 3+ net charge opioid tetrapeptide. Journal of Pharmacology and Experimental Therapeutics, 304, 425–432.PubMedCrossRefGoogle Scholar
  550. Zhao, X., Shang, T., Zhang, X., Ye, T., Wang, D., & Rei, L. (2016). Passage of Magnetic Tat-Conjugated Fe3O4@SiO2 nanoparticles across in vitro blood-brain barrier. Nanoscale Research Letters, 11, 451.PubMedPubMedCentralCrossRefGoogle Scholar
  551. Zhao, Y., Lou, D., Burkett, J., & Kohler, H. (2001). Chemical engineering of cell penetrating antibodies. Journal of Immunological Methods, 254, 137–145.CrossRefGoogle Scholar
  552. Zhou, Q. H., Hui, E. K., Lu, J. Z., Boado, R. J., & Pardridge, W. M. (2011a). Brain penetrating IgG-erythropoietin fusion protein is neuroprotective following intravenous treatment in Parkinson’s disease in the mouse. Brain Research, 25, 315–320.CrossRefGoogle Scholar
  553. Zhou, Q. H., Lu, J. Z., Hui, E. K., Boado, R. J., & Pardridge, W. M. (2011b). Delivery of a peptide radiopharmaceutical to brain with an IgG-avidin fusion protein. Bioconjugate Chemistry, 22, 1611–1618.PubMedPubMedCentralCrossRefGoogle Scholar
  554. Zhu, L., Kate, P., & Torchilin, V. P. (2012). Matrix metalloprotease 2-responsive multifunctional liposomal nanocarrier for enhanced tumor targeting. ACS Nano, 6, 3491–3498.PubMedPubMedCentralCrossRefGoogle Scholar
  555. Zhu, L., Wang, T., Perche, F., Taigind, A., & Torchilin, V. P. (2013). Enhanced anticancer activity of nanopreparation containing an MMP2-sensitive PEG-drug conjugate and cell-penetrating moiety. Proceedings of the National Academy of Sciences USA, 110, 17047–17052.CrossRefGoogle Scholar
  556. Ziemienowicz, A., Pepper, J., & Eudes, F. (2015). Applications of CPPs in genome modulation of plants. Methods Mol Biol, 1324, 417–434.PubMedCrossRefGoogle Scholar
  557. Ziemienowicz, A., Shim, Y. S., Matsuoka, A., Eudes, F., & Kovalchuk, I. (2012). A novel method of transgene delivery into triticale plants using the Agrobacterium transferred DNA-derived nano-complex. Plant Physiology, 158, 1503–1513.PubMedPubMedCentralCrossRefGoogle Scholar
  558. Zonin, E., Moscatiello, R., Miuzzo, M., Cavallarin, N., di Paolo, M. L., Sandona, D., et al. (2011). TAT-mediated aequorin transduction: An alternative approach for effective calcium measurements in plant cells. Plant and Cell Physiology, 52, 2225–2235.PubMedCrossRefGoogle Scholar
  559. Zou, Z., Sun, Z., Li, P., Feng, T., & Wu, S. (2016). Cre fused with RVG peptide mediates targeted genome editing in mouse brain cells in vivo. International Journal of Molecular Sciences, 17.Google Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.Department of Biochemistry and BiophysicsStockholm UniversityStockholmSweden
  2. 2.Institute of TechnologyUniversity of TartuTartuEstonia

Personalised recommendations