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Intracellular Delivery of Nanoparticles with CPPs

  • Rupa Sawant
  • Vladimir Torchilin
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 683)

Abstract

Cell-penetrating peptides (CPPs), in particular TATp, have been widely used for intracellular delivery of various cargoes, both in vitro and in vivo. Modifications of nanoparticles with CPPs require either covalent or noncovalent approach. Here we describe various methods to attach CPP, such as TATp to surface of nanocarriers (such as liposomes and micelles), loading with drug or DNA and characterization of same for in vitro and in vivo applications. Due to nonselectivity of CPPs and wide distribution in nontarget areas, method for preparation of “smart” nanocarrier with hidden TATp function is also described.

Key words

CPP Liposomes Micelles Nanoparticles “Smart” Drug Delivery System TATp pH sensitive DNA 

References

  1. 1.
    Deshayes, S., Morris, M. C., Divita, G., and Heitz, F. (2005) Cell-penetrating peptides: tools for intracellular delivery of therapeutics. Cell Mol Life Sci 62, 1839–1849.CrossRefPubMedGoogle Scholar
  2. 2.
    Joliot, A., Pernelle, C., Deagostini-Bazin, H., and Prochiantz, A. (1991) Antennapedia homeobox peptide regulates neural morphogenesis. Proc Natl Acad Sci U S A 88, 1864–1868.CrossRefPubMedGoogle Scholar
  3. 3.
    Elliott, G., and O’Hare, P. (1997) Intercellular trafficking and protein delivery by a herpesvirus structural protein. Cell 88, 223–233.CrossRefPubMedGoogle Scholar
  4. 4.
    Pooga, M., Hallbrink, M., Zorko, M., and Langel, Ü. (1998) Cell penetration by transportan. FASEB J 12, 67–77.PubMedGoogle Scholar
  5. 5.
    Oehlke, J., Scheller, A., Wiesner, B., Krause, E., Beyermann, M., Klauschenz, E., Melzig, M., and Bienert, M. (1998) Cellular uptake of an alpha-helical amphipathic model peptide with the potential to deliver polar compounds into the cell interior non-endocytically. Biochim Biophys Acta 1414, 127–139.CrossRefPubMedGoogle Scholar
  6. 6.
    Rojas, M., Donahue, J. P., Tan, Z., and Lin, Y. Z. (1998) Genetic engineering of proteins with cell membrane permeability. Nat Biotechnol 16, 370–375.CrossRefPubMedGoogle Scholar
  7. 7.
    Futaki, S., Suzuki, T., Ohashi, W., Yagami, T., Tanaka, S., Ueda, K., and Sugiura, Y. (2001) Arginine-rich peptides. An abundant source of membrane-permeable peptides having potential as carriers for intracellular protein delivery. J Biol Chem 276, 5836–5840.CrossRefPubMedGoogle Scholar
  8. 8.
    Gupta, B., Levchenko, T. S., and Torchilin, V. P. (2005) Intracellular delivery of large molecules and small particles by cell-penetrating proteins and peptides. Adv Drug Deliv Rev 57, 637–651.CrossRefPubMedGoogle Scholar
  9. 9.
    Josephson, L., Tung, C. H., Moore, A., and Weissleder, R. (1999) High-efficiency intracellular magnetic labeling with novel superparamagnetic-Tat peptide conjugates. Bioconjug Chem 10, 186–191.CrossRefPubMedGoogle Scholar
  10. 10.
    Rothbard, J. B., Jessop, T. C., and Wender, P. A. (2005) Adaptive translocation: the role of hydrogen bonding and membrane potential in the uptake of guanidinium-rich transporters into cells. Adv Drug Deliv Rev 57, 495–504.CrossRefPubMedGoogle Scholar
  11. 11.
    Fuchs, S. M., and Raines, R. T. (2004) Pathway for polyarginine entry into mammalian cells Biochemistry 43, 2438–2444.CrossRefPubMedGoogle Scholar
  12. 12.
    Fretz, M., Jin, J., Conibere, R., Penning, N. A., Al-Taei, S., Storm, G., Futaki, S., Takeuchi, T., Nakase, I., and Jones, A. T. (2006) Effects of Na+/H+ exchanger inhibitors on subcellular localisation of endocytic organelles and intracellular dynamics of protein transduction domains HIV-TAT peptide and octaarginine. J Control Release 116, 247–254.CrossRefPubMedGoogle Scholar
  13. 13.
    Snyder, E. L., and Dowdy, S. F. (2004) Cell penetrating peptides in drug delivery. Pharm Res 21, 389–393.CrossRefPubMedGoogle Scholar
  14. 14.
    Wadia, J. S., and Dowdy, S. F. (2005) Transmembrane delivery of protein and peptide drugs by TAT-mediated transduction in the treatment of cancer. Adv Drug Deliv Rev 57, 579–596.CrossRefPubMedGoogle Scholar
  15. 15.
    Rothbard, J. B., Garlington, S., Lin, Q., Kirschberg, T., Kreider, E., McGrane, P. L., Wender, P. A., and Khavari, P. A. (2000) Conjugation of arginine oligomers to cyclosporin A facilitates topical delivery and inhibition of inflammation. Nat Med 6, 1253–1257.CrossRefPubMedGoogle Scholar
  16. 16.
    Goun, E. A., Pillow, T. H., Jones, L. R., Rothbard, J. B., and Wender, P. A. (2006) Molecular transporters: synthesis of oligoguanidinium transporters and their application to drug delivery and real-time imaging Chembiochem 7, 1497–1515.CrossRefPubMedGoogle Scholar
  17. 17.
    Abes, S., Moulton, H. M., Clair, P., Prevot, P., Youngblood, D. S., Wu, R. P., Iversen, P. L., and Lebleu, B. (2006) Vectorization of morpholino oligomers by the (R-Ahx-R)4 peptide allows efficient splicing correction in the absence of endosomolytic agents. J Control Release 116, 304–313.Google Scholar
  18. 18.
    Abes, S., Turner, J. J., Ivanova, G. D., Owen, D., Williams, D., Arzumanov, A., Clair, P., Gait, M. J., and Lebleu, B. (2007) Efficient splicing correction by PNA conjugation to an R6-Penetratin delivery peptide. Nucleic Acids Res 35, 4495–4502.CrossRefPubMedGoogle Scholar
  19. 19.
    Meade, B. R., and Dowdy, S. F. (2007) Exogenous siRNA delivery using peptide transduction domains/cell penetrating peptides. Adv Drug Deliv Rev 59, 134–140.CrossRefPubMedGoogle Scholar
  20. 20.
    Meade, B. R., and Dowdy, S. F. (2008) Enhancing the cellular uptake of siRNA duplexes following noncovalent packaging with protein transduction domain peptides. Adv Drug Deliv Rev 60, 530–536.CrossRefPubMedGoogle Scholar
  21. 21.
    Jeang, K. T., Xiao, H., and Rich, E. A. (1999) Multifaceted activities of the HIV-1 transactivator of transcription, Tat. J Biol Chem 274, 28837–28840.CrossRefPubMedGoogle Scholar
  22. 22.
    Phelan, A., Elliott, G., and O’Hare, P. (1998) Intercellular delivery of functional p53 by the herpesvirus protein VP22. Nat Biotechnol 16, 440–443.CrossRefPubMedGoogle Scholar
  23. 23.
    Schwarze, S. R., Ho, A., Vocero-Akbani, A., and Dowdy, S. F. (1999) In vivo protein transduction: delivery of a biologically active protein into the mouse Science 285, 1569–1572.CrossRefPubMedGoogle Scholar
  24. 24.
    Cao, G., Pei, W., Ge, H., Liang, Q., Luo, Y., Sharp, F. R., Lu, A., Ran, R., Graham, S. H., and Chen, J. (2002) In vivo delivery of a Bcl-xL fusion protein containing the TAT protein transduction domain protects against ischemic brain injury and neuronal apoptosis. J Neurosci 22, 5423–5431.PubMedGoogle Scholar
  25. 25.
    Denicourt, C., and Dowdy, S. F. (2003) Protein transduction technology offers novel therapeutic approach for brain ischemia. Trends Pharmacol Sci 24, 216–218.PubMedGoogle Scholar
  26. 26.
    Astriab-Fisher, A., Sergueev, D., Fisher, M., Shaw, B. R., and Juliano, R. L. (2002) Conjugates of antisense oligonucleotides with the Tat and antennapedia cell-penetrating peptides: effects on cellular uptake, binding to target sequences, and biologic actions. Pharm Res 19, 744–754.CrossRefPubMedGoogle Scholar
  27. 27.
    Yang, S., Coles, D. J., Esposito, A., Mitchell, D. J., Toth, I., and Minchin, R. F. (2009) Cellular uptake of self-assembled cationic peptide-DNA complexes: multifunctional role of the enhancer chloroquine. J Control Release 135, 159–165.CrossRefPubMedGoogle Scholar
  28. 28.
    Trabulo, S., Mano, M., Faneca, H., Cardoso, A. L., Duarte, S., Henriques, A., Paiva, A., Gomes, P., Simoes, S., and de Lima, M. C. (2008) S4(13)-PV cell penetrating peptide and cationic liposomes act synergistically to mediate intracellular delivery of plasmid DNA. J Gene Med 10, 1210–1222.CrossRefPubMedGoogle Scholar
  29. 29.
    Fujita, T., Furuhata, M., Hattori, Y., Kawakami, H., Toma, K., and Maitani, Y. (2008) High gene delivery in tumor by intratumoral injection of tetraarginine-PEG lipid-coated protamine/DNA, J Control Release 129, 124–127.CrossRefPubMedGoogle Scholar
  30. 30.
    Zhao, M., Kircher, M. F., Josephson, L., and Weissleder, R. (2002) Differential conjugation of tat peptide to superparamagnetic nanoparticles and its effect on cellular uptake. Bioconjug Chem 13, 840–844.CrossRefPubMedGoogle Scholar
  31. 31.
    Lewin, M., Carlesso, N., Tung, C. H., Tang, X. W., Cory, D., Scadden, D. T., and Weissleder, R. (2000) Tat peptide-derivatized magnetic nanoparticles allow in vivo tracking and recovery of progenitor cells. Nat Biotechnol 18, 410–414.CrossRefPubMedGoogle Scholar
  32. 32.
    Zhang, K., Fang, H., Chen, Z., Taylor, J. S., and Wooley, K. L. (2008) Shape effects of nanoparticles conjugated with cell-penetrating peptides (HIV Tat PTD) on CHO cell uptake. Bioconjug Chem 19, 1880–1887.CrossRefPubMedGoogle Scholar
  33. 33.
    Berry, C. C., de la Fuente, J. M., Mullin, M., Chu, S. W., and Curtis, A. S. (2007) Nuclear localization of HIV-1 tat functionalized gold nanoparticles. IEEE Trans Nanobioscience 6, 262–269.CrossRefPubMedGoogle Scholar
  34. 34.
    Rao, K. S., Reddy, M. K., Horning, J. L., and Labhasetwar, V. (2008) TAT-conjugated nanoparticles for the CNS delivery of anti-HIV drugs Biomaterials 29, 4429–4438.CrossRefPubMedGoogle Scholar
  35. 35.
    Torchilin, V. P., Rammohan, R., Weissig, V., and Levchenko, T. S. (2001) TAT peptide on the surface of liposomes affords their efficient intracellular delivery even at low temperature and in the presence of metabolic inhibitors. Proc Natl Acad Sci U S A 98, 8786–8791.CrossRefPubMedGoogle Scholar
  36. 36.
    Fretz, M. M., Koning, G. A., Mastrobattista, E., Jiskoot, W., and Storm, G. (2004) OVCAR-3 cells internalize TAT-peptide modified liposomes by endocytosis. Biochim Biophys Acta 1665, 48–56.CrossRefPubMedGoogle Scholar
  37. 37.
    Levchenko, T. S., Rammohan, R., Volodina, N., and Torchilin, V. P. (2003) Tat peptide-mediated intracellular delivery of liposomes. Methods Enzymol 372, 339–349.CrossRefPubMedGoogle Scholar
  38. 38.
    Sethuraman, V. A., and Bae, Y. H. (2007) TAT peptide-based micelle system for potential active targeting of anti-cancer agents to acidic solid tumors. J Control Release 118, 216–224.CrossRefPubMedGoogle Scholar
  39. 39.
    Sawant, R. R., and Torchilin, V. P. (2009) Enhanced cytotoxicity of TATp-bearing paclitaxel-loaded micelles in vitro and in vivo. Int J Pharm 374, 114–118.CrossRefPubMedGoogle Scholar
  40. 40.
    Santra, S., Yang, H., Dutta, D., Stanley, J. T., Holloway, P. H., Tan, W., Moudgil, B. M., and Mericle, R. A. (2004) TAT conjugated, FITC doped silica nanoparticles for bioimaging applications. Chem Commun (Camb) (24), 2810–2811.Google Scholar
  41. 41.
    Mortensen, M. W., Bjorkdahl, O., Sorensen, P. G., Hansen, T., Jensen, M. R., Gundersen, H. J., and Bjornholm, T. (2006) Functionalization and cellular uptake of boron carbide nanoparticles. The first step toward T cell-guided boron neutron capture therapy. Bioconjug Chem 17, 284–290.CrossRefPubMedGoogle Scholar
  42. 42.
    Lasic, D. D. (1993) Liposomes: From Physics to Applications, Elsevier, Amsterdam.Google Scholar
  43. 43.
    Torchilin, V. P. (2005) Recent advances with liposomes as pharmaceutical carriers. Nat Rev Drug Discov 4, 145–160.CrossRefPubMedGoogle Scholar
  44. 44.
    Lasic, D. D., and Martin, F. J. (1995) Stealth Liposomes, CRC Press, Boca Raton.Google Scholar
  45. 45.
    Torchilin, V. P., Narula, J., Halpern, E., and Khaw, B. A. (1996) Poly(ethylene glycol)-coated anti-cardiac myosin immunoliposomes: factors influencing targeted accumulation in the infarcted myocardium. Biochim Biophys Acta 1279, 75–83.CrossRefPubMedGoogle Scholar
  46. 46.
    Torchilin, V. P., Levchenko, T. S., Lukyanov, A. N., Khaw, B. A., Klibanov, A. L., Rammohan, R., Samokhin, G. P., and Whiteman, K. R. (2001) p-Nitrophenylcarbonyl-PEG-PE-liposomes: fast and simple attachment of specific ligands, including monoclonal antibodies, to distal ends of PEG chains via p-nitrophenylcarbonyl groups. Biochim Biophys Acta 1511, 397–411.CrossRefPubMedGoogle Scholar
  47. 47.
    Torchilin, V. P. (2001) Structure and design of polymeric surfactant-based drug delivery systems. J Control Release 73, 137–172.CrossRefPubMedGoogle Scholar
  48. 48.
    Torchilin, V. P. (2007) Micellar nanocarriers: pharmaceutical perspectives. Pharm Res 24, 1–16.CrossRefPubMedGoogle Scholar
  49. 49.
    Maeda, H., Wu, J., Sawa, T., Matsumura, Y., and Hori, K. (2000) Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. J Control Release 65, 271–284.CrossRefPubMedGoogle Scholar
  50. 50.
    Maeda, H., Bharate, G. Y., and Daruwalla, J. (2009) Polymeric drugs for efficient tumor-targeted drug delivery based on EPR-effect. Eur J Pharm Biopharm 71, 409–419.CrossRefPubMedGoogle Scholar
  51. 51.
    Lukyanov, A. N., and Torchilin, V. P. (2004) Micelles from lipid derivatives of water-soluble polymers as delivery systems for poorly soluble drugs. Adv Drug Deliv Rev 56, 1273–1289.CrossRefPubMedGoogle Scholar
  52. 52.
    Lukyanov, A. N., Gao, Z., Mazzola, L., and Torchilin, V. P. (2002) Polyethylene glycol-diacyllipid micelles demonstrate increased accumulation in subcutaneous tumors in mice. Pharm Res 19, 1424–1429.CrossRefPubMedGoogle Scholar
  53. 53.
    Eum, W. S., Kim, D. W., Hwang, I. K., Yoo, K. Y., Kang, T. C., Jang, S. H., Choi, H. S., Choi, S. H., Kim, Y. H., Kim, S. Y., Kwon, H. Y., Kang, J. H., Kwon, O. S., Cho, S. W., Lee, K. S., Park, J., Won, M. H., and Choi, S. Y. (2004) In vivo protein transduction: biologically active intact pep-1-superoxide dismutase fusion protein efficiently protects against ischemic insult. Free Radic Biol Med 37, 1656–1669.CrossRefPubMedGoogle Scholar
  54. 54.
    Torchilin, V. P., Lukyanov, A. N., Gao, Z., and Papahadjopoulos-Sternberg, B. (2003) Immunomicelles: targeted pharmaceutical carriers for poorly soluble drugs. Proc Natl Acad Sci U S A 100, 6039–6044.CrossRefPubMedGoogle Scholar
  55. 55.
    Li, M., Chrastina, A., Levchenko, T., and Torchilin, V. P. (2005) Micelles from poly(ethylene glycol)-phosphatidyl ethanolamine conjugates (PEG-PE) as pharmaceutical nanocarriers for poorly soluble drug camptothecin. J Biomed Nanotechnol 1, 190–195.CrossRefGoogle Scholar
  56. 56.
    Tseng, Y. L., Liu, J. J., and Hong, R. L. (2002) Translocation of liposomes into cancer cells by cell-penetrating peptides penetratin and tat: a kinetic and efficacy study. Mol Pharmacol 62, 864–872.CrossRefPubMedGoogle Scholar
  57. 57.
    Torchilin, V. P., Levchenko, T. S., Rammohan, R., Volodina, N., Papahadjopoulos-Sternberg, B., and D’Souza, G. G. (2003) Cell transfection in vitro and in vivo with nontoxic TAT peptide-liposome-DNA complexes. Proc Natl Acad Sci U S A 100, 1972–1977.CrossRefPubMedGoogle Scholar
  58. 58.
    Gupta, B., Levchenko, T. S., and Torchilin, V. P. (2007) TAT peptide-modified liposomes provide enhanced gene delivery to intracranial human brain tumor xenografts in nude mice. Oncol Res 16, 351–359.PubMedGoogle Scholar
  59. 59.
    Pappalardo, J. S., Quattrocchi, V., Langellotti, C., Di Giacomo, S., Gnazzo, V., Olivera, V., Calamante, G., Zamorano, P. I., Levchenko, T. S., and Torchilin, V. P. (2009) Improved transfection of spleen-derived antigen-presenting cells in culture using TATp-liposomes. J Control Release 134, 41–46.CrossRefPubMedGoogle Scholar
  60. 60.
    Stroh, M., Zimmer, J. P., Duda, D. G., Levchenko, T. S., Cohen, K. S., Brown, E. B., Scadden, D. T., Torchilin, V. P., Bawendi, M. G., Fukumura, D., and Jain, R. K. (2005) Quantum dots spectrally distinguish multiple species within the tumor milieu in vivo. Nat Med 11, 678–682.CrossRefPubMedGoogle Scholar
  61. 61.
    Cryan, S. A., Devocelle, M., Moran, P. J., Hickey, A. J., and Kelly, J. G. (2006) Increased intracellular targeting to airway cells using octaarginine-coated liposomes: in vitro assessment of their suitability for inhalation. Mol Pharm 3, 104–112.CrossRefPubMedGoogle Scholar
  62. 62.
    Yagi, N., Yano, Y., Hatanaka, K., Yokoyama, Y., and Okuno, H. (2007) Synthesis and evaluation of a novel lipid-peptide conjugate for functionalized liposome. Bioorg Med Chem Lett 17, 2590–2593.CrossRefPubMedGoogle Scholar
  63. 63.
    Zhang, C., Tang, N., Liu, X., Liang, W., Xu, W., and Torchilin, V. P. (2006) siRNA-containing liposomes modified with polyarginine effectively silence the targeted gene. J Control Release 112, 229–239.CrossRefPubMedGoogle Scholar
  64. 64.
    Ko, Y. T., Hartner, W. C., Kale, A., and Torchilin, V. P. (2009) Gene delivery into ischemic myocardium by double-targeted lipoplexes with anti-myosin antibody and TAT peptide. Gene Ther 16, 52–59.CrossRefPubMedGoogle Scholar
  65. 65.
    Dodd, C. H., Hsu, H. C., Chu, W. J., Yang, P., Zhang, H. G., Mountz, J. D., Jr., Zinn, K., Forder, J., Josephson, L., Weissleder, R., Mountz, J. M., and Mountz, J. D. (2001) Normal T-cell response and in vivo magnetic resonance imaging of T cells loaded with HIV transactivator-peptide-derived superparamagnetic nanoparticles. J Immunol Methods 256, 89–105.CrossRefPubMedGoogle Scholar
  66. 66.
    Sawant, R. R., Sawant, R. M., Kale, A. A., and Torchilin, V. P. (2008) The architecture of ligand attachment to nanocarriers controls their specific interaction with target cells. J Drug Target 16, 596–600.CrossRefPubMedGoogle Scholar
  67. 67.
    Tkachenko, A. G., Xie, H., Liu, Y., Coleman, D., Ryan, J., Glomm, W. R., Shipton, M. K., Franzen, S., and Feldheim, D. L. (2004) Cellular trajectories of peptide-modified gold particle complexes: comparison of nuclear localization signals and peptide transduction domains. Bioconjug Chem 15, 482–490.CrossRefPubMedGoogle Scholar
  68. 68.
    de la Fuente, J. M., and Berry, C. C. (2005) Tat peptide as an efficient molecule to translocate gold nanoparticles into the cell nucleus. Bioconjug Chem 16, 1176–1180.CrossRefPubMedGoogle Scholar
  69. 69.
    Suk, J. S., Suh, J., Choy, K., Lai, S. K., Fu, J., and Hanes, J. (2006) Gene delivery to differentiated neurotypic cells with RGD and HIV Tat peptide functionalized polymeric nanoparticles Biomaterials 27, 5143–5150.CrossRefPubMedGoogle Scholar
  70. 70.
    Kleemann, E., Neu, M., Jekel, N., Fink, L., Schmehl, T., Gessler, T., Seeger, W., and Kissel, T. (2005) Nano-carriers for DNA delivery to the lung based upon a TAT-derived peptide covalently coupled to PEG-PEI. J Control Release 109, 299–316.CrossRefPubMedGoogle Scholar
  71. 71.
    Nguyen, J., Xie, X., Neu, M., Dumitrascu, R., Reul, R., Sitterberg, J., Bakowsky, U., Schermuly, R., Fink, L., Schmehl, T., Gessler, T., Seeger, W., and Kissel, T. (2008) Effects of cell-penetrating peptides and pegylation on transfection efficiency of polyethylenimine in mouse lungs. J Gene Med 10, 1236–1246.CrossRefPubMedGoogle Scholar
  72. 72.
    Mae, M., El Andaloussi, S., Lundin, P., Oskolkov, N., Johansson, H. J., Guterstam, P., and Langel, U. (2009) A stearylated CPP for delivery of splice correcting oligonucleotides using a non-covalent co-incubation strategy. J Control Release 134, 221–227.CrossRefPubMedGoogle Scholar
  73. 73.
    Zorko, M., and Langel, U. (2005) Cell-penetrating peptides: mechanism and kinetics of cargo delivery. Adv Drug Deliv Rev 57, 529–545.CrossRefPubMedGoogle Scholar
  74. 74.
    Kaplan, I. M., Wadia, J. S., and Dowdy, S. F. (2005) Cationic TAT peptide transduction domain enters cells by macropinocytosis. J Control Release 102, 247–253.CrossRefPubMedGoogle Scholar
  75. 75.
    Derossi, D., Calvet, S., Trembleau, A., Brunissen, A., Chassaing, G., and Prochiantz, A. (1996) Cell internalization of the third helix of the Antennapedia homeodomain is receptor-independent. J Biol Chem 271, 18188–18193.CrossRefPubMedGoogle Scholar
  76. 76.
    Hyndman, L., Lemoine, J. L., Huang, L., Porteous, D. J., Boyd, A. C., and Nan, X. (2004) HIV-1 Tat protein transduction domain peptide facilitates gene transfer in combination with cationic liposomes. J Control Release 99, 435–444.CrossRefPubMedGoogle Scholar
  77. 77.
    Khalil, I. A., Kogure, K., Futaki, S., Hama, S., Akita, H., Ueno, M., Kishida, H., Kudoh, M., Mishina, Y., Kataoka, K., Yamada, M., and Harashima, H. (2007) Octaarginine-modified multifunctional envelope-type nanoparticles for gene delivery. Gene Ther 14, 682–689.CrossRefPubMedGoogle Scholar
  78. 78.
    Yamada, Y., Akita, H., Kamiya, H., Kogure, K., Yamamoto, T., Shinohara, Y., Yamashita, K., Kobayashi, H., Kikuchi, H., and Harashima, H. (2008) MITO-Porter: A liposome-based carrier system for delivery of macromolecules into mitochondria via membrane fusion. Biochim Biophys Acta 1778, 423–432.CrossRefPubMedGoogle Scholar
  79. 79.
    Wadia, J. S., Stan, R. V., and Dowdy, S. F. (2004) Transducible TAT-HA fusogenic peptide enhances escape of TAT-fusion proteins after lipid raft macropinocytosis. Nat Med 10, 310–315.CrossRefPubMedGoogle Scholar
  80. 80.
    El-Andaloussi, S., Johansson, H. J., Lundberg, P., and Langel, U. (2006) Induction of splice correction by cell-penetrating peptide nucleic acids. J Gene Med 8, 1262–1273.CrossRefPubMedGoogle Scholar
  81. 81.
    Plank, C., Oberhauser, B., Mechtler, K., Koch, C., and Wagner, E. (1994) The influence of endosome-disruptive peptides on gene transfer using synthetic virus-like gene transfer systems. J Biol Chem 269, 12918–12924.PubMedGoogle Scholar
  82. 82.
    Sugita, T., Yoshikawa, T., Mukai, Y., Yamanada, N., Imai, S., Nagano, K., Yoshida, Y., Shibata, H., Yoshioka, Y., Nakagawa, S., Kamada, H., Tsunoda, S., and Tsutsumi, Y. (2007) Improved cytosolic translocation and tumor-killing activity of Tat-shepherdin conjugates mediated by co-treatment with Tat-fused endosome-disruptive HA2 peptide. Biochem Biophys Res Commun 363, 1027–1032.CrossRefPubMedGoogle Scholar
  83. 83.
    Moore, N. M., Sheppard, C. L., and Sakiyama-Elbert, S. E. (2009) Characterization of a multifunctional PEG-based gene delivery system containing nuclear localization signals and endosomal escape peptides. Acta Biomater 5, 854–864.CrossRefPubMedGoogle Scholar
  84. 84.
    Sirsi, S. R., Schray, R. C., Guan, X., Lykens, N. M., Williams, J. H., Erney, M. L., and Lutz, G. J. (2008) Functionalized PEG-PEI copolymers complexed to exon-skipping oligonucleotides improve dystrophin expression in mdx mice. Hum Gene Ther 19, 795–806.CrossRefPubMedGoogle Scholar
  85. 85.
    Shiraishi, T., Pankratova, S., and Nielsen, P. E. (2005) Calcium ions effectively enhance the effect of antisense peptide nucleic acids conjugated to cationic tat and oligoarginine peptides. Chem Biol 12, 923–929.CrossRefPubMedGoogle Scholar
  86. 86.
    Shiraishi, T., and Nielsen, P. E. (2006) Enhanced delivery of cell-penetrating peptide-peptide nucleic acid conjugates by endosomal disruption. Nat Protoc 1, 633–636.CrossRefPubMedGoogle Scholar
  87. 87.
    Futaki, S., Ohashi, W., Suzuki, T., Niwa, M., Tanaka, S., Ueda, K., Harashima, H., and Sugiura, Y. (2001) Stearylated arginine-rich peptides: a new class of transfection systems. Bioconjug Chem 12, 1005–1011.CrossRefPubMedGoogle Scholar
  88. 88.
    Tonges, L., Lingor, P., Egle, R., Dietz, G. P., Fahr, A., and Bahr, M. (2006) Stearylated octaarginine and artificial virus-like particles for transfection of siRNA into primary rat neurons. RNA 12, 1431–1438.CrossRefPubMedGoogle Scholar
  89. 89.
    Sawant, R. M., Hurley, J. P., Salmaso, S., Kale, A., Tolcheva, E., Levchenko, T. S., and Torchilin, V. P. (2006) “SMART” drug delivery systems: double-targeted pH-responsive pharmaceutical nanocarriers. Bioconjug Chem 17, 943–949.CrossRefPubMedGoogle Scholar
  90. 90.
    Kale, A. A., and Torchilin, V. P. (2007) Design, synthesis, and characterization of pH-sensitive PEG-PE conjugates for stimuli-sensitive pharmaceutical nanocarriers: the effect of substitutes at the hydrazone linkage on the pH stability of PEG-PE conjugates. Bioconjug Chem 18, 363–370.CrossRefPubMedGoogle Scholar
  91. 91.
    Kale, A. A., and Torchilin, V. P. (2007) Enhanced transfection of tumor cells in vivo using “Smart” pH-sensitive TAT-modified pegylated liposomes. J Drug Target 15, 538–545.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Rupa Sawant
    • 1
  • Vladimir Torchilin
    • 2
  1. 1.Research Associate Center for Pharmaceutical Biotechnology and NanomedicineNortheastern UniversityBostonUSA
  2. 2.Center for Pharmaceutical, Biotechnology and NanomedicineNortheastern UniversityBostonUSA

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