Journal of Pharmaceutical Investigation

, Volume 47, Issue 3, pp 203–227 | Cite as

Surface modification of lipid-based nanocarriers for cancer cell-specific drug targeting

  • Chang Hyun Kim
  • Sang Gon Lee
  • Myung Joo Kang
  • Sangkil Lee
  • Young Wook Choi


Targeted drug delivery systems using nanocarriers for anticancer drugs have been investigated for over several decades. Among the many nanocarrier systems, lipid-based nanocarriers such as liposomes, solid lipid nanoparticles, and nanostructured lipid carriers have afforded attention as a carrier system to improve the efficacy of anticancer drugs. Recent efforts have focused on cancer cell-specific drug delivery through the functionalization of the surface of lipid-based nanocarriers with various ligands such as targeting moieties, cell-penetrating peptides, and cell-penetrating homing peptides to overcome non-selectivity, minimize side effects, and enhance antitumor efficacy. However, the use of ligand modification has been limited because the nanocarriers were easily recognized by the mononuclear phagocyte system and thus rapidly removed from the blood circulation. To achieve prolonged systemic circulation, nanocarriers were further modified with protective polymers such as polyethylene glycol (PEG). Unexpectedly, this presented a PEG dilemma, as the interaction of ligands with the target was hindered and induced poor cellular uptake. Recently, stimuli-sensitive cleavage of the PEG coat, following recognition of the cancer cell microclimate, such as low pH, redox-potential, and over-expressed enzymes, was established to solve this problem. This review presents a comprehensive overview on the current state of surface-modified lipid-based nanocarriers for the improved delivery of anticancer drugs.


Lipid-based nanocarriers Surface modification Cancer targeting Intracellular delivery PEGylation Stimuli-sensitivity 



This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (No. 2016R1A2B4011449). The authors also appreciate the scholarship given to Sang Gon Lee from the Health Fellowship Foundation.

Compliance with ethical standards

Conflict of the interest

All authors (C.H. Kim, S.G. Lee, M.J. Kang, S. Lee, and Y.W. Choi) declare that they have no conflict of interest.


  1. Accardo A, Salsano G, Morisco A, Aurilio M, Parisi A, Maione F, Morelli G (2012) Peptide-modified liposomes for selective targeting of bombesin receptors overexpressed by cancer cells: a potential theranostic agent. Int J Nanomedicine 7:2007–2017PubMedPubMedCentralGoogle Scholar
  2. Akhtar MJ, Ahamed M, Alhadlaq HA, Alrokayan SA, Kumar S (2014) Targeted anticancer therapy: overexpressed receptors and nanotechnology. Clin Chim Acta 436:78–92PubMedCrossRefGoogle Scholar
  3. Al-Ahmady ZS, Chaloin O, Kostarelos K (2014) Monoclonal antibody-targeted, temperature-sensitive liposomes: in vivo tumor chemotherapeutics in combination with mild hyperthermia. J Control Release 196:332–343PubMedCrossRefGoogle Scholar
  4. Amin M, Badiee A, Jaafari MR (2013) Improvement of pharmacokinetic and antitumor activity of PEGylated liposomal doxorubicin by targeting with N-methylated cyclic RGD peptide in mice bearing C-26 colon carcinomas. Int J Pharm 458:324–333PubMedCrossRefGoogle Scholar
  5. Arpicco S, Lerda C, Dalla Pozza E, Costanzo C, Tsapis N, Stella B, Palmieri M (2013) Hyaluronic acid-coated liposomes for active targeting of gemcitabine. Eur J Pharm Biopharm 85:373–380PubMedCrossRefGoogle Scholar
  6. Awada A, Bondarenko IN, Bonneterre J, Nowara E, Ferrero JM, Bakshi AV, CT4002 Study Group (2014) A randomized controlled phase II trial of a novel composition of paclitaxel embedded into neutral and cationic lipids targeting tumor endothelial cells in advanced triple-negative breast cancer (TNBC). Ann Oncol 25:824–831PubMedCrossRefGoogle Scholar
  7. Banerjee R, Tyagi P, Li S, Huang L (2004) Anisamide-targeted stealth liposomes: a potent carrier for targeting doxorubicin to human prostate cancer cells. Int J Cancer 112:693–700PubMedCrossRefGoogle Scholar
  8. Bao A, Phillips WT, Goins B, Zheng X, Sabour S, Natarajan M, Ross Woolley F, Zavaleta C, Otto RA (2006) Potential use of drug carried-liposomes for cancer therapy via direct intratumoral injection. Int J Pharm 316:162–169PubMedCrossRefGoogle Scholar
  9. Bashyal S, Noh G, Keum T, Choi YW, Lee S (2016) Cell penetrating peptides as an innovative approach for drug delivery; then, present and the future. J Pharm Invest 46:205–220CrossRefGoogle Scholar
  10. Benhabbour SR, Sheardown H, Adronov A (2008) Protein resistance of PEG-functionalized dendronized surfaces: effect of PEG molecular weight and dendron generation. Macromolecules 41:4817–4823CrossRefGoogle Scholar
  11. Bertrand N, Wu J, Xu X, Kamaly N, Farokhzad OC (2014) Cancer nanotechnology: the impact of passive and active targeting in the era of modern cancer biology. Adv Drug Deliv Rev 66:2–25PubMedCrossRefGoogle Scholar
  12. Bidlingmaier S, He J, Wang Y, An F, Feng J, Barbone D, Liu B (2009) Identification of MCAM/CD146 as the target antigen of a human monoclonal antibody that recognizes both epithelioid and sarcomatoid types of mesothelioma. Cancer Res 69:1570–1577PubMedPubMedCentralCrossRefGoogle Scholar
  13. Biswas S, Deshpande PP, Perche F, Dodwadkar NS, Sane SD, Torchilin VP (2013a) Octa-arginine-modified pegylated liposomal doxorubicin: an effective treatment strategy for non-small cell lung cancer. Cancer Lett 335:191–200PubMedPubMedCentralCrossRefGoogle Scholar
  14. Biswas S, Dodwadkar NS, Deshpande PP, Parab S, Torchilin VP (2013b) Surface functionalization of doxorubicin-loaded liposomes with octa-arginine for enhanced anticancer activity. Eur J Pharm Biopharm 84:517–525PubMedPubMedCentralCrossRefGoogle Scholar
  15. Bondì ML, Craparo EF, Giammona G, Cervello M, Azzolina A, Diana P, Martorana A, Cirrincione G (2007) Nanostructured lipid carriers-containing anticancer compounds: preparation, characterization, and cytotoxicity studies. Drug Deliv 14:61–67PubMedCrossRefGoogle Scholar
  16. Brannon-Peppas L, Blanchette JO (2012) Nanoparticle and targeted systems for cancer therapy. Adv Drug Deliv Rev 64:206–212CrossRefGoogle Scholar
  17. Brown JM, Wilson WR (2004) Exploiting tumour hypoxia in cancer treatment. Nat Rev Cancer 4:437–447PubMedCrossRefGoogle Scholar
  18. Bruun J, Larsen TB, Jølck RI, Eliasen R, Holm R, Gjetting T, Andresen TL (2015) Investigation of enzyme-sensitive lipid nanoparticles for delivery of siRNA to blood-brain barrier and glioma cells. Int J Nanomedicine 10:5995–6008PubMedPubMedCentralGoogle Scholar
  19. Cai L, Wang X, Wang W, Qiu N, Wen J, Duan X, Wei Y (2012) Peptide ligand and PEG-mediated long-circulating liposome targeted to FGFR overexpressing tumor in vivo. Int J Nanomedicine 7:4499–4510PubMedPubMedCentralGoogle Scholar
  20. Cai D, Gao W, He B, Dai W, Zhang H, Wang X, Zhang Q (2014) Hydrophobic penetrating peptide PFVYLI-modified stealth liposomes for doxorubicin delivery in breast cancer therapy. Biomaterials 35:2283–2294PubMedCrossRefGoogle Scholar
  21. Chang M, Lu S, Zhang F, Zuo T, Guan Y, Wei T, Lin G (2015) RGD-modified pH-sensitive liposomes for docetaxel tumor targeting. Colloids Surf B Biointerf 129:175–182CrossRefGoogle Scholar
  22. Chen DB, Yang TZ, Wang-Liang LU, Zhang Q (2001) In vitro and in vivo study of two types of long-circulating solid lipid nanoparticles containing paclitaxel. Chem Pharm Bull 49:1444–1447PubMedCrossRefGoogle Scholar
  23. Chen Y, Sen J, Bathula SR, Yang Q, Fittipaldi R, Huang L (2009) Novel cationic lipid that delivers siRNA and enhances therapeutic effect in lung cancer cells. Mol Pharm 6:696–705PubMedPubMedCentralCrossRefGoogle Scholar
  24. Chen D, Jiang X, Huang Y, Zhang C, Ping Q (2010a) pH-sensitive mPEG-Hz-cholesterol conjugates as a liposome delivery system. J Bioact Compat Polym 25:527–542CrossRefGoogle Scholar
  25. Chen H, Tang L, Qin Y, Yin Y, Tang J, Tang W, He Q (2010b) Lactoferrin-modified procationic liposomes as a novel drug carrier for brain delivery. Eur J Pharm Sci 40:94–102PubMedCrossRefGoogle Scholar
  26. Chen X, Wang X, Wang Y, Hu J, Yang L, Xiao W, Fu A, Cai L, Li X, Ye X, Liu Y, Wu W, Shao X, Mao Y, Yang Lwei Y, Chen L (2010c) Improved tumor-targeting drug delivery and therapeutic efficacy by cationic liposome modified with truncated bFGF peptide. J Controll Release 145:17–25CrossRefGoogle Scholar
  27. Chen D, Liu W, Shen Y, Mu H, Zhang Y, Liang R, Fu F (2011a) Effects of a novel pH-sensitive liposome with cleavable esterase-catalyzed and pH-responsive double smart mPEG lipid derivative on ABC phenomenon. Int J Nanomedicine 6:2053–2061PubMedPubMedCentralCrossRefGoogle Scholar
  28. Chen H, Qin Y, Zhang Q, Jiang W, Tang L, Liu J, He Q (2011b) Lactoferrin modified doxorubicin-loaded procationic liposomes for the treatment of gliomas. Eur J Pharm Sci 44:164–173PubMedCrossRefGoogle Scholar
  29. Chen J, Chen H, Cui S, Xue B, Tian J, Achilefu S, Gu Y (2012) Glucosamine derivative modified nanostructured lipid carriers for targeted tumor delivery. J Mater Chem 22:5770–5783CrossRefGoogle Scholar
  30. Cheng L, Huang FZ, Cheng LF, Zhu YQ, Hu Q, Li L, Chen DW (2014) GE11-modified liposomes for non-small cell lung cancer targeting: preparation, ex vitro and in vivo evaluation. Int J Nanomedicine 9:921–935PubMedPubMedCentralCrossRefGoogle Scholar
  31. Chono S, Li SD, Conwell CC, Huang L (2008) An efficient and low immunostimulatory nanoparticle formulation for systemic siRNA delivery to the tumor. J Control Release 131:64–69PubMedPubMedCentralCrossRefGoogle Scholar
  32. Chou LY, Ming K, Chan WC (2011) Strategies for the intracellular delivery of nanoparticles. Chem Soc Rev 40:233–245PubMedCrossRefGoogle Scholar
  33. Copolovici DM, Langel K, Eriste E, Langel U (2014) Cell-penetrating peptides: design, synthesis, and applications. ACS Nano 8:1972–1994PubMedCrossRefGoogle Scholar
  34. Dai W, Jin W, Zhang J, Wang X, Wang J, Zhang X, Zhang Q (2012) Spatiotemporally controlled co-delivery of anti-vasculature agent and cytotoxic drug by octreotide-modified stealth liposomes. Pharm Res 29:2902–2911PubMedCrossRefGoogle Scholar
  35. Dams ET, Laverman P, Oyen WJ, Storm G, Scherphof GL, van der Meer JW, Boerman OC (2000) Accelerated blood clearance and altered biodistribution of repeated injections of sterically stabilized liposomes. J Pharmacol Exp Ther 292:1071–1079PubMedGoogle Scholar
  36. De La Rica R, Aili D, Stevens MM (2012) Enzyme-responsive nanoparticles for drug release and diagnostics. Adv Drug Deliv Rev 64:967–978CrossRefGoogle Scholar
  37. Demeule M, Currie JC, Bertrand Y, Che C, Nguyen T, Regina A, Beliveau R (2008) Involvement of the low-density lipoprotein receptor-related protein in the transcytosis of the brain delivery vector Angiopep-2. J Neurochem 106:1534–1544PubMedCrossRefGoogle Scholar
  38. Ding Y, Sun D, Wang GL, Yang HG, Xu HF, Chen JH, Wang ZQ (2015) An efficient PEGylated liposomal nanocarrier containing cell-penetrating peptide and pH-sensitive hydrazone bond for enhancing tumor-targeted drug delivery. Int J Nanomedicine 10:6199–6214PubMedPubMedCentralGoogle Scholar
  39. Drummond DC, Meyer O, Hong K, Kirpotin DB, Papahadjopoulos D (1999) Optimizing liposomes for delivery of chemotherapeutic agents to solid tumors. Pharmacol Rev 51:691–744PubMedGoogle Scholar
  40. Du J, Li L (2016) Which one performs better for targeted lung cancer combination therapy: pre-or post-bombesin-decorated nanostructured lipid carriers? Drug Deliv 23:1799–1809PubMedCrossRefGoogle Scholar
  41. Du J, Lane LA, Nie S (2015) Stimuli-responsive nanoparticles for targeting the tumor microenvironment. J Control Release 219:205–214PubMedPubMedCentralCrossRefGoogle Scholar
  42. Duncan R (2003) The dawning era of polymer therapeutics. Nat Rev Drug Discov 2:347–360PubMedCrossRefGoogle Scholar
  43. Fillebeen C, Descamps L, Dehouck MP, Fenart L, Benaı̈ssa M, Spik G, Pierce A (1999) Receptor-mediated transcytosis of lactoferrin through the blood-brain barrier. J Biol Chem 274:7011–7017PubMedCrossRefGoogle Scholar
  44. Fishman MN, Elsayed Y, Damjanov N, Steinberg JL, Mahany JJ, Nieves JA, Sherman JW (2004) Phase I study of liposome entrapped paclitaxel (LEP-ETU) in patients with advanced cancer. J Clin Oncol 22:2110–2110CrossRefGoogle Scholar
  45. Fundarò A, Cavalli R, Bargoni A, Vighetto D, Zara GP, Gasco MR (2000) Non-stealth and stealth solid lipid nanoparticles (SLN) carrying doxorubicin: pharmacokinetics and tissue distribution after iv administration to rats. Pharmacol Res 42:337–343PubMedCrossRefGoogle Scholar
  46. Furuhata M, Izumisawa T, Kawakami H, Toma K, Hattori Y, Maitani Y (2009) Decaarginine-PEG-liposome enhanced transfection efficiency and function of arginine length and PEG. Int J Pharm 371:40–46PubMedCrossRefGoogle Scholar
  47. Gaillard PJ, Appeldoorn CC, Dorland R, van Kregten J, Manca F, Vugts DJ, van Tellingen O (2014) Pharmacokinetics, brain delivery, and efficacy in brain tumor-bearing mice of glutathione pegylated liposomal doxorubicin (2B3-101). PloS ONE 9:e82331PubMedPubMedCentralCrossRefGoogle Scholar
  48. Gao J, Sun J, Li H, Liu W, Zhang Y, Li B, Guo Y (2010) Lyophilized HER2-specific PEGylated immunoliposomes for active siRNA gene silencing. Biomaterials 31:2655–2664PubMedCrossRefGoogle Scholar
  49. Gao J, Liu W, Xia Y, Li W, Sun J, Chen H, Deng L (2011) The promotion of siRNA delivery to breast cancer overexpressing epidermal growth factor receptor through anti-EGFR antibody conjugation by immunoliposomes. Biomaterials 32:3459–3470PubMedCrossRefGoogle Scholar
  50. Gao J, Yu Y, Zhang Y, Song J, Chen H, Li W, Qian W, Deng L, Kou G, Chen J, Guo Y (2012) EGFR-specific PEGylated immunoliposomes for active siRNA delivery in hepatocellular carcinoma. Biomaterials 33:270–282PubMedCrossRefGoogle Scholar
  51. Garg A, Tisdale AW, Haidari E, Kokkoli E (2009) Targeting colon cancer cells using PEGylated liposomes modified with a fibronectin-mimetic peptide. Int J Pharm 366:201–210PubMedCrossRefGoogle Scholar
  52. Gerweck LE, Seetharaman K (1996) Cellular pH gradient in tumor versus normal tissue: potential exploitation for the treatment of cancer. Cancer Res 56:1194–1198PubMedGoogle Scholar
  53. Gill PS, Wernz J, Scadden DT, Cohen P, Mukwaya GM, von Roenn JH, Rarick MU (1996) Randomized phase III trial of liposomal daunorubicin versus doxorubicin, bleomycin, and vincristine in AIDS-related Kaposi’s sarcoma. J Clin Oncol 14:2353–2364PubMedCrossRefGoogle Scholar
  54. Ginn C, Khalili H, Lever R, Brocchini S (2014) PEGylation and its impact on the design of new protein-based medicines. Future Med Chem 6:1829–1846PubMedCrossRefGoogle Scholar
  55. Gordon AN, Fleagle JT, Guthrie D, Parkin DE, Gore ME, Lacave AJ (2001) Recurrent epithelial ovarian carcinoma: a randomized phase III study of pegylated liposomal doxorubicin versus topotecan. J Clin Oncol 19:3312–3322PubMedCrossRefGoogle Scholar
  56. Goutayer M, Dufort S, Josserand V, Royère A, Heinrich E, Vinet F, Texier I (2010) Tumor targeting of functionalized lipid nanoparticles: assessment by in vivo fluorescence imaging. Eur J Pharm Biopharm 75:137–147PubMedCrossRefGoogle Scholar
  57. Gullotti E, Yeo Y (2009) Extracellularly activated nanocarriers: a new paradigm of tumor targeted drug delivery. Mol Pharm 6:1041–1051PubMedPubMedCentralCrossRefGoogle Scholar
  58. Guo Z, He B, Jin H, Zhang H, Dai W, Zhang L, Zhang Q (2014) Targeting efficiency of RGD-modified nanocarriers with different ligand intervals in response to integrin αvβ3 clustering. Biomaterials 35:6106–6117PubMedCrossRefGoogle Scholar
  59. Gupta B, Torchilin VP (2007) Monoclonal antibody 2C5-modified doxorubicin-loaded liposomes with significantly enhanced therapeutic activity against intracranial human brain U-87 MG tumor xenografts in nude mice. Cancer Immunol Immunother 56:1215–1223PubMedCrossRefGoogle Scholar
  60. Han Y, Zhang Y, Li D, Chen Y, Sun J, Kong F (2014) Transferrin-modified nanostructured lipid carriers as multifunctional nanomedicine for codelivery of DNA and doxorubicin. Int J Nanomedicine 9:4107–4116PubMedPubMedCentralGoogle Scholar
  61. Hatakeyama H, Akita H, Kogure K, Oishi M, Nagasaki Y, Kihira Y, Harashima H (2007) Development of a novel systemic gene delivery system for cancer therapy with a tumor-specific cleavable PEG-lipid. Gene Ther 14:68–77PubMedCrossRefGoogle Scholar
  62. Hatakeyama H, Akita H, Ito E, Hayashi Y, Oishi M, Nagasaki Y, Baba Y (2011) Systemic delivery of siRNA to tumors using a lipid nanoparticle containing a tumor-specific cleavable PEG-lipid. Biomaterials 32:4306–4316PubMedCrossRefGoogle Scholar
  63. He Y, Zhang L, Song C (2010) Luteinizing hormone-releasing hormone receptor-mediated delivery of mitoxantrone using LHRH analogs modified with PEGylated liposomes. Int J Nanomedicine 5:697–705PubMedPubMedCentralGoogle Scholar
  64. Hobbs SK, Monsky WL, Yuan F, Roberts WG, Griffith L, Torchilin VP, Jain RK (1998) Regulation of transport pathways in tumor vessels: role of tumor type and microenvironment. Proc Natl Acad Sci U S A 95:4607–4612PubMedPubMedCentralCrossRefGoogle Scholar
  65. Hong RL, Huang CJ, Tseng YL, Pang VF, Chen ST, Liu JJ, Chang FH (1999) Direct comparison of liposomal doxorubicin with or without polyethylene glycol coating in C-26 tumor-bearing mice. Clin Cancer Res 5:3645–3652PubMedGoogle Scholar
  66. Hou C, Tu Z, Mach R, Kung HF, Kung MP (2006) Characterization of a novel iodinated sigma-2 receptor ligand as a cell proliferation marker. Nucl Med Biol 33:203–209PubMedCrossRefGoogle Scholar
  67. Hu Q, Katti PS, Gu Z (2014) Enzyme-responsive nanomaterials for controlled drug delivery. Nanoscale 6:12273–12286PubMedPubMedCentralCrossRefGoogle Scholar
  68. Immordino ML, Brusa P, Arpicco S, Stella B, Dosio F, Cattel L (2003) Preparation, characterization, cytotoxicity and pharmacokinetics of liposomes containing docetaxel. J Control Release 91:417–429PubMedCrossRefGoogle Scholar
  69. Immordino ML, Dosio F, Cattel L (2006) Stealth liposomes: review of the basic science, rationale, and clinical applications, existing and potential. Int J Nanomedicine 1:297–315PubMedPubMedCentralCrossRefGoogle Scholar
  70. Ishida T, Maeda R, Ichihara M, Mukai Y, Motoki Y, Manabe Y, Kiwada H (2002) The accelerated clearance on repeated injection of pegylated liposomes in rats: laboratory and histopathological study. Cell Mol Biol Lett 7:286–286PubMedGoogle Scholar
  71. Iwamaru Y, Shimizu Y, Imamura M, Murayama Y, Endo R, Tagawa Y, Yokoyama T (2008) Lactoferrin induces cell surface retention of prion protein and inhibits prion accumulation. J Neurochem 107:636–646PubMedCrossRefGoogle Scholar
  72. Iwase Y, Maitani Y (2011) Octreotide-targeted liposomes loaded with CPT-11 enhanced cytotoxicity for the treatment of medullary thyroid carcinoma. Mol Pharm 8:330–337PubMedCrossRefGoogle Scholar
  73. Iyer AK, Su Y, Feng J, Lan X, Zhu X, Liu Y, Liu B (2011) The effect of internalizing human single chain antibody fragment on liposome targeting to epithelioid and sarcomatoid mesothelioma. Biomaterials 32:2605–2613PubMedPubMedCentralCrossRefGoogle Scholar
  74. Jain A, Agarwal A, Majumder S, Lariya N, Khaya A, Agrawal H, Agrawal GP (2010) Mannosylated solid lipid nanoparticles as vectors for site-specific delivery of an anti-cancer drug. J Control Release 148:359–367PubMedCrossRefGoogle Scholar
  75. Jain A, Kesharwani P, Garg NK, Jain A, Jain SA, Jain AK, Katare OP (2015) Galactose engineered solid lipid nanoparticles for targeted delivery of doxorubicin. Colloids Surf B Biointerf 134:47–58CrossRefGoogle Scholar
  76. Jiang J, Yang SJ, Wang JC, Yang LJ, Xu ZZ, Yang T, Zhang Q (2010) Sequential treatment of drug-resistant tumors with RGD-modified liposomes containing siRNA or doxorubicin. Eur J Pharm Biopharm 76:170–178PubMedCrossRefGoogle Scholar
  77. Joshi MD, Müller RH (2009) Lipid nanoparticles for parenteral delivery of actives. Eur J Pharm Biopharm 71:161–172PubMedCrossRefGoogle Scholar
  78. Kang MJ, Park SH, Kang MH, Park MJ, Choi YW (2013) Folic acid-tethered Pep-1 peptide-conjugated liposomal nanocarrier for enhanced intracellular drug delivery to cancer cells: conformational characterization and in vitro cellular uptake evaluation. Int J Nanomedicine 8:1155–1165PubMedPubMedCentralCrossRefGoogle Scholar
  79. Kang MH, Park MJ, Yoo HJ, Lee SG, Kim SR, Yeom DW, Kang MJ, Choi YW (2014) RIPL peptide (IPLVVPLRRRRRRRRC)-conjugated liposomes for enhanced intracellular drug delivery to hepsin-expressing cancer cells. Eur J Pharm Biopharm 87:489–499PubMedCrossRefGoogle Scholar
  80. Kang MH, Yoo HJ, Kwon YH, Yoon HY, Lee SG, Kim SR, Choi YW (2015) Design of multifunctional liposomal nanocarriers for folate receptor-specific intracellular drug delivery. Mol Pharm 12:4200–4213PubMedCrossRefGoogle Scholar
  81. Khajavinia A, Varshosaz J, Dehkordi AJ (2012) Targeting etoposide to acute myelogenous leukemia cells using nanostructured lipid carriers coated with transferrin. Nanotechnology 23:1–13CrossRefGoogle Scholar
  82. Khalid MN, Simard P, Hoarau D, Dragomir A, Leroux JC (2006) Long circulating poly (ethylene glycol)-decorated lipid nanocapsules deliver docetaxel to solid tumors. Pharm Res 23:752–758PubMedCrossRefGoogle Scholar
  83. Kibria G, Hatakeyama H, Ohga N, Hida K, Harashima H (2011) Dual-ligand modification of PEGylated liposomes shows better cell selectivity and efficient gene delivery. J Control Release 153:141–148PubMedCrossRefGoogle Scholar
  84. Kim IY, Kang YS, Lee DS, Park HJ, Choi EK, Oh YK, Kim JS (2009) Antitumor activity of EGFR targeted pH-sensitive immunoliposomes encapsulating gemcitabine in A549 xenograft nude mice. J Control Release 140:55–60PubMedCrossRefGoogle Scholar
  85. Kim HK, Thompson DH, Jang HS, Chung YJ, Van den Bossche J (2013) pH-responsive biodegradable assemblies containing tunable phenyl-substituted vinyl ethers for use as efficient gene delivery vehicles. ACS Appl Mater Interfaces 5:5648–5658PubMedPubMedCentralCrossRefGoogle Scholar
  86. Ko AH, Tempero MA, Shan YS, Su WC, Lin YL, Dito E, Chen LT (2013) A multinational phase 2 study of nanoliposomal irinotecan sucrosofate (PEP02, MM-398) for patients with gemcitabine-refractory metastatic pancreatic cancer. Br J Cancer 109:920–925PubMedPubMedCentralCrossRefGoogle Scholar
  87. Kobayashi T, Ishida T, Okada Y, Ise S, Harashima H, Kiwada H (2007) Effect of transferrin receptor-targeted liposomal doxorubicin in P-glycoprotein-mediated drug resistant tumor cells. Int J Pharm 329:94–102PubMedCrossRefGoogle Scholar
  88. Koren E, Apte A, Jani A, Torchilin VP (2012) Multifunctional PEGylated 2C5-immunoliposomes containing pH-sensitive bonds and TAT peptide for enhanced tumor cell internalization and cytotoxicity. J Control Release 160:264–273PubMedCrossRefGoogle Scholar
  89. Koshkaryev A, Piroyan A, Torchilin VP (2012) Increased apoptosis in cancer cells in vitro and in vivo by ceramides in transferrin-modified liposomes. Cancer Biol Ther 13:50–60PubMedPubMedCentralCrossRefGoogle Scholar
  90. Kuai R, Yuan W, Li W, Qin Y, Tang J, Yuan M, He Q (2011) Targeted delivery of cargoes into a murine solid tumor by a cell-penetrating peptide and cleavable poly (ethylene glycol) comodified liposomal delivery system via systemic administration. Mol Pharm 8:2151–2161PubMedCrossRefGoogle Scholar
  91. Kulkarni PS, Haldar MK, Nahire RR, Katti P, Ambre AH, Muhonen WW, Shrivastava DK (2014) MMP-9 responsive PEG cleavable nanovesicles for efficient delivery of chemotherapeutics to pancreatic cancer. Mol Pharm 11:2390–2399PubMedPubMedCentralCrossRefGoogle Scholar
  92. Kwon YH, Shin TH, Jang MH, Yoon HY, Kang MH, Kang MJ, Choi YW (2017) Surface-modification of RIPL peptide-conjugated liposomes to achieve steric stabilization and pH sensitivity. J Nanosci Nanotechnol 17:1008–1017Google Scholar
  93. Lammers T, Kiessling F, Hennink WE, Storm G (2012) Drug targeting to tumors: principles, pitfalls and (pre-) clinical progress. J Control Release 161:175–187PubMedCrossRefGoogle Scholar
  94. Landesman-Milo D, Goldsmith M, Ben-Arye SL, Witenberg B, Brown E, Leibovitch S, Peer D (2013) Hyaluronan grafted lipid-based nanoparticles as RNAi carriers for cancer cells. Cancer Lett 334:221–227PubMedCrossRefGoogle Scholar
  95. Leamon CP, Reddy JA (2004) Folate-targeted chemotherapy. Adv Drug Deliv Rev 56(8):1127–1141PubMedCrossRefGoogle Scholar
  96. Li SD, Huang L (2010) Stealth nanoparticles: high density but sheddable PEG is a key for tumor targeting. J Control Release 145:178–181PubMedPubMedCentralCrossRefGoogle Scholar
  97. Li X, Ding L, Xu Y, Wang Y, Ping Q (2009a) Targeted delivery of doxorubicin using stealth liposomes modified with transferrin. Int J Pharm 373:116–123PubMedCrossRefGoogle Scholar
  98. Li X, Wang D, Zhang J, Pan W (2009b) Preparation and pharmacokinetics of docetaxel based on nanostructured lipid carriers. J Pharm Pharmacol 61:1485–1492PubMedCrossRefGoogle Scholar
  99. Li X, Tian T, Zhang J, Zhao X, Chen X, Jiang Y, Wang D, Pan W (2011) In vitro and in vivo evaluation of folate receptor-targeting amphiphilic copolymer modified liposomes loaded with docetaxel. Int J Nanomedicine 6:1167–1184PubMedPubMedCentralGoogle Scholar
  100. Li Y, Lee RJ, Yu K, Bi Y, Qi Y, Sun Y, Teng L (2016) Delivery of siRNA using lipid nanoparticles modified with cell penetrating peptide. ACS Appl Mater Interfaces 8:26613–26621PubMedCrossRefGoogle Scholar
  101. Liu D, Zhang N (2010) Cancer chemotherapy with lipid-based nanocarriers. Crit Rev Ther Drug Carrier Syst 27(:):371–417PubMedGoogle Scholar
  102. Liu D, Liu F, Liu Z, Wang L, Zhang N (2011) Tumor specific delivery and therapy by double-targeted nanostructured lipid carriers with anti-VEGFR-2 antibody. Mol Pharm 8:2291–2301PubMedCrossRefGoogle Scholar
  103. Liu Y, Ran R, Chen J, Kuang Q, Tang J, Mei L, He Q (2014) Paclitaxel loaded liposomes decorated with a multifunctional tandem peptide for glioma targeting. Biomaterials 35:4835–4847PubMedCrossRefGoogle Scholar
  104. Liu Y, Mei L, Yu Q, Xu C, Qiu Y, Yang Y, Shi K, Zhang Q, Gao H, Zhang Z, He Q (2015) Multifunctional tandem peptide modified paclitaxel-loaded liposomes for the treatment of vasculogenic mimicry and cancer stem cells in malignant glioma. ACS Appl Mater Interfaces 7:16792–16801PubMedCrossRefGoogle Scholar
  105. Liu R, Li X, Xiao W, Lam KS (2016) Tumor-targeting peptides from combinatorial libraries. Adv Drug Deliv Rev. doi: 10.1016/j.addr.2016.05.009 Google Scholar
  106. Lozano N, Al-Ahmady ZS, Beziere NS, Ntziachristos V, Kostarelos K (2015) Monoclonal antibody-targeted PEGylated liposome-ICG encapsulating doxorubicin as a potential theranostic agent. Int J Pharm 482:2–10PubMedCrossRefGoogle Scholar
  107. Luria-Pérez R, Helguera G, Rodríguez JA (2016) Antibody-mediated targeting of the transferrin receptor in cancer cells. Boletín Médico del Hospital Infantil de México 73:372–379CrossRefGoogle Scholar
  108. Madhankumar AB, Slagle-Webb B, Wang X, Yang QX, Antonetti DA, Miller PA, Sheehan JM, Connor JR (2009) Efficacy of interleukin-13 receptor–targeted liposomal doxorubicin in the intracranial brain tumor model. Mol Cancer Ther 8:648–654PubMedCrossRefGoogle Scholar
  109. Maeda H, Nakamura H, Fang J (2013) The EPR effect for macromolecular drug delivery to solid tumors: improvement of tumor uptake, lowering of systemic toxicity, and distinct tumor imaging in vivo. Adv Drug Deliv Rev 65:71–79PubMedCrossRefGoogle Scholar
  110. Mamot C, Ritschard R, Vogel B, Dieterle T, Bubendorf L, Hilker C, Rochlitz C (2011) A phase I study of doxorubicin-loaded anti-EGFR immunoliposomes in patients with advanced solid tumors. J Clin Oncol 29:3029–3029CrossRefGoogle Scholar
  111. Mansour AM, Drevs J, Esser N, Hamada FM, Badary OA, Unger C, Kratz F (2003) A new approach for the treatment of malignant melanoma: enhanced antitumor efficacy of an albumin-binding doxorubicin prodrug that is cleaved by matrix metalloproteinase 2. Cancer Res 63:4062–4066PubMedGoogle Scholar
  112. Marasco D, Perretta G, Sabatella M, Ruvo M (2008) Past and future perspectives of synthetic peptide libraries. Curr Protein Pept Sci 9:447–467PubMedCrossRefGoogle Scholar
  113. Maruyama K (2011) Intracellular targeting delivery of liposomal drugs to solid tumors based on EPR effects. Adv Drug Deliv Rev 63:161–169PubMedCrossRefGoogle Scholar
  114. Mattheolabakis G, Milane L, Singh A, Amiji MM (2015) Hyaluronic acid targeting of CD44 for cancer therapy: from receptor biology to nanomedicine. J Drug Target 23:605–618PubMedCrossRefGoogle Scholar
  115. McNeeley KM, Karathanasis E, Annapragada AV, Bellamkonda RV (2009) Masking and triggered unmasking of targeting ligands on nanocarriers to improve drug delivery to brain tumors. Biomaterials 30:3986–3995PubMedCrossRefGoogle Scholar
  116. Mehnert W, Mäder K (2001) Solid lipid nanoparticles: production, characterization and applications. Adv Drug Deliv Rev 47:165–196PubMedCrossRefGoogle Scholar
  117. Mei L, Fu L, Shi K, Zhang Q, Liu Y, Tang J, He Q (2014) Increased tumor targeted delivery using a multistage liposome system functionalized with RGD TAT and cleavable PEG. Int J Pharm 468:26–38PubMedCrossRefGoogle Scholar
  118. Mishra S, Webster P, Davis ME (2004) PEGylation significantly affects cellular uptake and intracellular trafficking of non-viral gene delivery particles. Eur J Cell Biol 83:97–111PubMedCrossRefGoogle Scholar
  119. Mishra B, Patel BB, Tiwari S (2010) Colloidal nanocarriers: a review on formulation technology, types and applications toward targeted drug delivery. Nanomedicine 6:9–24PubMedCrossRefGoogle Scholar
  120. Mo R, Gu Z (2016) Tumor microenvironment and intracellular signal-activated nanomaterials for anticancer drug delivery. Mater Today 19 :274–283CrossRefGoogle Scholar
  121. Mohammadi Ghalaei P, Varshosaz J, Sadeghi Aliabadi H (2014) Evaluating cytotoxicity of hyaluronate targeted solid lipid nanoparticles of etoposide on SK-OV-3 cells. J Drug Deliv 7:1–7CrossRefGoogle Scholar
  122. Müller RH, Radtke M, Wissing SA (2002a) Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) in cosmetic and dermatological preparations. Adv Drug Deliv Rev 54:S131–S155PubMedCrossRefGoogle Scholar
  123. Müller RH, Radtke M, Wissing SA (2002b) Nanostructured lipid matrices for improved microencapsulation of drugs. Int J Pharm 242:121–128PubMedCrossRefGoogle Scholar
  124. Muthu MS, Kulkarni SA, Raju A, Feng SS (2012) Theranostic liposomes of TPGS coating for targeted co-delivery of docetaxel and quantum dots. Biomaterials 33:3494–3501PubMedCrossRefGoogle Scholar
  125. Nakamura Y, Kogure K, Futaki S, Harashima H (2007) Octaarginine-modified multifunctional envelope-type nano device for siRNA. J Control Release 11:360–367CrossRefGoogle Scholar
  126. Navarro G, Movassaghian S, Torchilin VP (2014) Multifunctional nanocarriers for tumor drug delivery and imaging In: Mitra AK (ed) Drug delivery, 1st edn. Jones & Bartlett learning, Burlington, pp 157–187Google Scholar
  127. Necas J, Bartosikova L, Brauner P, Kolar J (2008) Hyaluronic acid (hyaluronan): a review. Vet Med (Praha) 53 :397–411Google Scholar
  128. Negussie AH, Miller JL, Reddy G, Drake SK, Wood BJ, Dreher MR (2010) Synthesis and in vitro evaluation of cyclic NGR peptide targeted thermally sensitive liposome. J Control Release 143:265–273PubMedPubMedCentralCrossRefGoogle Scholar
  129. Oumzil K, Khiati S, Grinstaff MW, Barthélémy P (2011) Reduction-triggered delivery using nucleoside-lipid based carriers possessing a cleavable PEG coating. J Control Release 151:123–130PubMedCrossRefGoogle Scholar
  130. Owens DE, Peppas NA (2006) Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles. Int J Pharm 307:93–102PubMedCrossRefGoogle Scholar
  131. Paliwal SR, Paliwal R, Mishra N, Mehta A, Vyas SP (2010) A novel cancer targeting approach based on estrone anchored stealth liposome for site-specific breast cancer therapy. Curr Cancer Drug Targets 10:343–353PubMedCrossRefGoogle Scholar
  132. Paliwal SR, Paliwal R, Pal HC, Saxena AK, Sharma PR, Gupta PN, Vyas SP (2011) Estrogen-anchored pH-sensitive liposomes as nanomodule designed for site-specific delivery of doxorubicin in breast cancer therapy. Mol Pharm 9:176–186PubMedCrossRefGoogle Scholar
  133. Pardeike J, Hommoss A, Müller RH (2009) Lipid nanoparticles (SLN, NLC) in cosmetic and pharmaceutical dermal products. Int J Pharm 366:170–184PubMedCrossRefGoogle Scholar
  134. Patel DK, Tripathy S, Nair SK, Kesharwani R (2013) Nanostructured lipid carrier (NLC) a modern approach for topical delivery: a review. World J Pharm Pharma Sci 2:921–938Google Scholar
  135. Perche F, Biswas S, Wang T, Zhu L, Torchilin VP (2014) Hypoxia targeted siRNA delivery. Angew Chem Int Ed Engl 53:3362–3366PubMedPubMedCentralCrossRefGoogle Scholar
  136. Qhattal HSS, Liu X (2011) Characterization of CD44-mediated cancer cell uptake and intracellular distribution of hyaluronan-grafted liposomes. Mol Pharm 8:1233–1246PubMedPubMedCentralCrossRefGoogle Scholar
  137. Qin Y, Chen H, Yuan W, Kuai R, Zhang Q, Xie F, He Q (2011a) Liposome formulated with TAT-modified cholesterol for enhancing the brain delivery. Int J Pharm 419:85–95PubMedCrossRefGoogle Scholar
  138. Qin Y, Chen H, Zhang Q, Wang X, Yuan W, Kuai R, Liu J (2011b) Liposome formulated with TAT-modified cholesterol for improving brain delivery and therapeutic efficacy on brain glioma in animals. Int J Pharm 420:304–312PubMedCrossRefGoogle Scholar
  139. Qu CY, Zhou M, Chen YW, Chen MM, Shen F, Xu LM (2015) Engineering of lipid prodrug-based, hyaluronic acid-decorated nanostructured lipid carriers platform for 5-fluorouracil and cisplatin combination gastric cancer therapy. Int J Nanomedicine 10:3911–3920PubMedPubMedCentralGoogle Scholar
  140. Ravar F, Saadat E, Gholami M, Dehghankelishadi P, Mahdavi M, Azami S, Dorkoosh FA (2016) Hyaluronic acid-coated liposomes for targeted delivery of paclitaxel, in-vitro characterization and in-vivo evaluation. J Control Release 229:10–22PubMedCrossRefGoogle Scholar
  141. Reddy LH, Sharma RK, Chuttani K, Mishra AK, Murthy RR (2004) Etoposide-incorporated tripalmitin nanoparticles with different surface charge: formulation, characterization, radiolabeling, and biodistribution studies. AAPS J 6:55–64PubMedCentralCrossRefGoogle Scholar
  142. Remaut K, Lucas B, Braeckmans K, Demeester J, De Smedt SC (2007) Pegylation of liposomes favours the endosomal degradation of the delivered phosphodiester oligonucleotides. J Control Release 117:256–266PubMedCrossRefGoogle Scholar
  143. Rodriguez BL, Blando JM, Lansakara PD, Kiguchi Y, DiGiovanni J, Cui Z (2013) Antitumor activity of tumor-targeted RNA replicase-based plasmid that expresses interleukin-2 in a murine melanoma model. Mol Pharm 10:2404–2415PubMedPubMedCentralCrossRefGoogle Scholar
  144. Romberg B, Hennink WE, Storm G (2008) Sheddable coatings for long-circulating nanoparticles. Pharm Res 25:55–71PubMedCrossRefGoogle Scholar
  145. Ross JS, Schenkein DP, Pietrusko R, Rolfe M, Linette GP, Stec J, Hortobagyi GN (2004) Targeted therapies for cancer 2004. Am J Clin Pathol 122:598–609PubMedCrossRefGoogle Scholar
  146. Sakurai Y, Hatakeyama H, Sato Y, Hyodo M, Akita H, Ohga N, Harashima H (2014) RNAi-mediated gene knockdown and anti-angiogenic therapy of RCCs using a cyclic RGD-modified liposomal-siRNA system. J Control Release 173:110–118PubMedCrossRefGoogle Scholar
  147. Sankhala KK, Mita AC, Adinin R, Wood L, Beeram M, Bullock S, Phan A (2009) A phase I pharmacokinetic (PK) study of MBP-426, a novel liposome encapsulated oxaliplatin. J Clin Oncol 27(:):2535Google Scholar
  148. Sanna V, Pala N, Sechi M (2014) Targeted therapy using nanotechnology: focus on cancer. Int J Nanomedicine 9:467–483PubMedPubMedCentralGoogle Scholar
  149. Scherphof GL, Dijkstra JAN, Spanjer HH, Derksen JT, Roerdink FH (1985) Uptake and intracellular processing of targeted and nontargeted liposomes by Rat Kupffer Cells in vivo and in vitro. Ann N Y Acad Sci 446:368–384PubMedCrossRefGoogle Scholar
  150. Shan D, Li J, Cai P, Prasad P, Liu F, Rauth AM, Wu XY (2015) RGD-conjugated solid lipid nanoparticles inhibit adhesion and invasion of αvβ3 integrin-overexpressing breast cancer cells. Drug Deliv Transl Res 5:15–26PubMedCrossRefGoogle Scholar
  151. Shao Z, Shao J, Tan B, Guan S, Liu Z, Zhao Z, Zhao J (2015) Targeted lung cancer therapy: preparation and optimization of transferrin-decorated nanostructured lipid carriers as novel nanomedicine for co-delivery of anticancer drugs and DNA. Int J Nanomedicine 10:1223–1233PubMedPubMedCentralCrossRefGoogle Scholar
  152. Shehata T, Ogawara K, Higaki K, Kimura T (2008) Prolongation of residence time of liposome by surface-modification with mixture of hydrophilic polymers. Int J Pharm 359:272–279PubMedCrossRefGoogle Scholar
  153. Shen H, Shi S, Zhang Z, Gong T, Sun X (2015) Coating solid lipid nanoparticles with hyaluronic acid enhances antitumor activity against melanoma stem-like cells. Theranostics 5 :755–771PubMedPubMedCentralCrossRefGoogle Scholar
  154. Shi C, Gao F, Gao X, Liu Y (2015) A novel anti-VEGF165 monoclonal antibody-conjugated liposomal nanocarrier system: physical characterization and cellular uptake evaluation in vitro and in vivo. Biomed Pharmacother 69:191–200PubMedCrossRefGoogle Scholar
  155. Shmeeda H, Tzemach D, Mak L, Gabizon A (2009) Her2-targeted pegylated liposomal doxorubicin: retention of target-specific binding and cytotoxicity after in vivo passage. J Control Release 136:155–160PubMedCrossRefGoogle Scholar
  156. Shmeeda H, Amitay Y, Gorin Y, Tzemach D, Mak L, Ogorka J, Kumar S, Zhang JA, Gabizon A (2010) Delivery of zoledronic acid encapsulated in folate-targeted liposome results in potent in vitro cytotoxic activity on tumor cells. J Control Release 146:76–83PubMedCrossRefGoogle Scholar
  157. Sinha R, Kim GJ, Nie S, Shin D (2006) Nanotechnology in cancer therapeutics: bioconjugated nanoparticles for drug delivery. Mol Cancer Ther 5:1909–1917PubMedCrossRefGoogle Scholar
  158. Song S, Mao G, Du J, Zhu X (2016) Novel RGD containing, temozolomide-loading nanostructured lipid carriers for glioblastoma multiforme chemotherapy. Drug Deliv 23:1404–1408PubMedCrossRefGoogle Scholar
  159. Srinivasarao M, Galliford CV, Low PS (2015) Principles in the design of ligand-targeted cancer therapeutics and imaging agents. Nat Rev Drug Discov 14:203–219PubMedCrossRefGoogle Scholar
  160. Steichen SD, Caldorera-Moore M, Peppas NA (2013) A review of current nanoparticle and targeting moieties for the delivery of cancer therapeutics. Eur J Pharm Sci 48:416–427PubMedCrossRefGoogle Scholar
  161. Su Z, Niu J, Xiao Y, Ping Q, Sun M, Huang A, Yuan D (2011) Effect of octreotide–polyethylene glycol (100) monostearate modification on the pharmacokinetics and cellular uptake of nanostructured lipid carrier loaded with hydroxycamptothecine. Mol Pharm 8:1641–1651PubMedCrossRefGoogle Scholar
  162. Su Z, Shi Y, Xiao Y, Sun M, Ping Q, Zong L, Chen Y (2013) Effect of octreotide surface density on receptor-mediated endocytosis in vitro and anticancer efficacy of modified nanocarrier in vivo after optimization. Int J Pharm 447:281–292PubMedCrossRefGoogle Scholar
  163. Sudimack J, Lee RJ (2000) Targeted drug delivery via the folate receptor. Adv Drug Deliv Rev 41:147–162PubMedCrossRefGoogle Scholar
  164. Sun M, Gao Y, Zhu Z, Wang H, Han C, Yang X, Pan W (2016) A systematic in vitro investigation on poly-arginine modified nanostructured lipid carrier: pharmaceutical characteristics, cellular uptake, mechanisms and cytotoxicity. Asian J Pharm Sci 12:51–58CrossRefGoogle Scholar
  165. Tang J, Zhang L, Fu H, Kuang Q, Gao H, Zhang Z, He Q (2014) A detachable coating of cholesterol-anchored PEG improves tumor targeting of cell-penetrating peptide-modified liposomes. Acta Pharm Sin B 4 :67–73PubMedPubMedCentralCrossRefGoogle Scholar
  166. Taratula O, Kuzmov A, Shah M, Garbuzenko OB, Minko T (2013) Nanostructured lipid carriers as multifunctional nanomedicine platform for pulmonary co-delivery of anticancer drugs and siRNA. J Control Release 171:349–357PubMedPubMedCentralCrossRefGoogle Scholar
  167. Tavano L, Muzzalupo R (2016) Multi-functional vesicles for cancer therapy: the ultimate magic bullet. Colloids Surf B Biointerf 147:161–171CrossRefGoogle Scholar
  168. Temsamani J, Vidal P (2004) The use of cell-penetrating peptides for drug delivery. Drug Discov Today 9:1012–1019PubMedCrossRefGoogle Scholar
  169. Terada T, Iwai M, Kawakami S, Yamashita F, Hashida M (2006) Novel PEG-matrix metalloproteinase-2 cleavable peptide-lipid containing galactosylated liposomes for hepatocellular carcinoma-selective targeting. J Control Release 111:333–342PubMedCrossRefGoogle Scholar
  170. Torchilin VP (2008) Tat peptide-mediated intracellular delivery of pharmaceutical nanocarriers. Adv Drug Deliv Rev 60:548–558PubMedCrossRefGoogle Scholar
  171. Torchilin VP (2009) Multifunctional and stimuli-sensitive pharmaceutical nanocarriers. Eur J Pharm Biopharm 71:431–444PubMedCrossRefGoogle Scholar
  172. Torchilin VP (2014) Multifunctional, stimuli-sensitive nanoparticulate systems for drug delivery. Nat Rev Drug Discov 13:813–827PubMedPubMedCentralCrossRefGoogle Scholar
  173. Trabulo S, Cardoso AL, Mano M, De Lima MCP (2010) Cell-penetrating peptides—mechanisms of cellular uptake and generation of delivery systems. Pharmaceuticals 3:961–993PubMedPubMedCentralCrossRefGoogle Scholar
  174. Tran TH, Choi JY, Ramasamy T, Truong DH, Nguyen CN, Choi HG, Kim JO (2014) Hyaluronic acid-coated solid lipid nanoparticles for targeted delivery of vorinostat to CD44 overexpressing cancer cells. Carbohydr Polym 114:407–415PubMedCrossRefGoogle Scholar
  175. Ucar E, Teksoz S, Ichedef C, Kilcar AY, Medine EI, Ari K, Unak P (2017) Synthesis, characterization and radiolabeling of folic acid modified nanostructured lipid carriers as a contrast agent and drug delivery system. Appl Radiat Isot 119:72–79PubMedCrossRefGoogle Scholar
  176. Üner M (2006) Preparation, characterization and physico-chemical properties of solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC): their benefits as colloidal drug carrier systems. Pharmazie 61:375–386PubMedGoogle Scholar
  177. Üner M, Yener G (2007) Importance of solid lipid nanoparticles (SLN) in various administration routes and future perspectives. Int J Nanomedicine 2:289–300PubMedPubMedCentralGoogle Scholar
  178. Vllasaliu D, Fowler R, Stolnik S (2014) PEGylated nanomedicines: recent progress and remaining concerns. Expert Opin Drug Deliv 11:139–154PubMedCrossRefGoogle Scholar
  179. Walkey CD, Olsen JB, Guo H, Emili A, Chan WC (2012) Nanoparticle size and surface chemistry determine serum protein adsorption and macrophage uptake. J Am Chem Soc 134:2139–2147PubMedCrossRefGoogle Scholar
  180. Wan F, You J, Sun Y, Zhang XG, Cui FD, Du YZ, Yuan H, Hu FQ (2008) Studies on PEG-modified SLNs loading vinorelbine bitartrate (I): preparation and evaluation in vitro. Int J Pharm 359:104–110PubMedCrossRefGoogle Scholar
  181. Wan Y, Han J, Fan G, Zhang Z, Gong T, Sun X (2013) Enzyme-responsive liposomes modified adenoviral vectors for enhanced tumor cell transduction and reduced immunogenicity. Biomaterials 34:3020–3030PubMedCrossRefGoogle Scholar
  182. Wang L, Su W, Liu Z, Zhou M, Chen S, Chen Y, Han Z (2012) CD44 antibody-targeted liposomal nanoparticles for molecular imaging and therapy of hepatocellular carcinoma. Biomaterials 33:5107–5114PubMedCrossRefGoogle Scholar
  183. Wang RH, Cao HM, Tian ZJ, Jin B, Wang Q, Ma H, Wu J (2015) Efficacy of dual-functional liposomes containing paclitaxel for treatment of lung cancer. Oncol Rep 33:783–791PubMedGoogle Scholar
  184. Webb BA, Chimenti M, Jacobson MP, Barber DL (2011) Dysregulated pH: a perfect storm for cancer progression. Nat Rev Cancer 11:671–677PubMedCrossRefGoogle Scholar
  185. Wei M, Xu Y, Zou Q, Tu L, Tang C, Xu T, Wu C (2012) Hepatocellular carcinoma targeting effect of PEGylated liposomes modified with lactoferrin. Eur J Pharm Sci 46:131–141PubMedCrossRefGoogle Scholar
  186. Wicki A, Rochlitz C, Orleth A, Ritschard R, Albrecht I, Herrmann R, Mamot C (2012) Targeting tumor-associated endothelial cells: anti-VEGFR2 immunoliposomes mediate tumor vessel disruption and inhibit tumor growth. Clin Cancer Res 18:454–464PubMedCrossRefGoogle Scholar
  187. Wicki A, Witzigmann D, Balasubramanian V, Huwyler J (2015) Nanomedicine in cancer therapy: challenges, opportunities, and clinical applications. J Control Release 200:138–157PubMedCrossRefGoogle Scholar
  188. Wissing SA, Kayser O, Müller RH (2004) Solid lipid nanoparticles for parenteral drug delivery. Adv Drug Deliv Rev 56:1257–1272PubMedCrossRefGoogle Scholar
  189. Wu L, Tang C, Yin C (2010) Folate-mediated solid–liquid lipid nanoparticles for paclitaxel-coated poly(ethylene glycol). Drug Dev Ind Pharm 36:439–448PubMedCrossRefGoogle Scholar
  190. Xu S, Olenyuk BZ, Okamoto CT, Hamm-Alvarez SF (2013a) Targeting receptor-mediated endocytotic pathways with nanoparticles: rationale and advances. Adv Drug Deliv Rev 65:121–138PubMedCrossRefGoogle Scholar
  191. Xu X, Wang L, Xu HQ, Huang XE, Qian YD, Xiang J (2013b) Clinical comparison between paclitaxel liposome (Lipusu®) and paclitaxel for treatment of patients with metastatic gastric cancer. Asian Pac J Cancer Prev 14:2591–2594PubMedCrossRefGoogle Scholar
  192. Yang XY, Li YX, Li M, Zhang L, Feng LX, Zhang N (2013) Hyaluronic acid-coated nanostructured lipid carriers for targeting paclitaxel to cancer. Cancer Lett 334:338–345PubMedCrossRefGoogle Scholar
  193. Yang G, Yang T, Zhang W, Lu M, Ma X, Xiang G (2014a) In vitro and in vivo antitumor effects of folate-targeted ursolic acid Stealth liposome. J Agric Food Chem 62:2207–2215PubMedCrossRefGoogle Scholar
  194. Yang ZZ, Li JQ, Wang ZZ, Dong DW, Qi XR (2014b) Tumor-targeting dual peptides-modified cationic liposomes for delivery of siRNA and docetaxel to gliomas. Biomaterials 35:5226–5239PubMedCrossRefGoogle Scholar
  195. Ye P, Zhang W, Yang T, Lu Y, Lu M, Gai Y, Ma X, Xiang G (2014) Folate receptor-targeted liposomes enhanced the antitumor potency of imatinib through the combination of active targeting and molecular targeting. Int J Nanomedicine 9:2167–2178PubMedPubMedCentralCrossRefGoogle Scholar
  196. Yuan L, Liu C, Chen Y, Zhang Z, Zhou L, Qu D (2013) Antitumor activity of tripterine via cell-penetrating peptide-coated nanostructured lipid carriers in a prostate cancer model. Int J Nanomedicine 8:4339–4350PubMedPubMedCentralGoogle Scholar
  197. Yuan M, Qiu Y, Zhang L, Gao H, He Q (2016) Targeted delivery of transferrin and TAT co-modified liposomes encapsulating both paclitaxel and doxorubicin for melanoma. Drug Deliv 23:1171–1183PubMedGoogle Scholar
  198. Zagar TM, Vujaskovic Z, Formenti S, Rugo H, Muggia F, O’Connor B, Straube W (2014) Two phase I dose-escalation/pharmacokinetics studies of low temperature liposomal doxorubicin (LTLD) and mild local hyperthermia in heavily pretreated patients with local regionally recurrent breast cancer. Int J Hyperthermia 30:285–294PubMedPubMedCentralCrossRefGoogle Scholar
  199. Zara GP, Bargoni A, Cavalli R, Fundarò A, Vighetto D, Gasco MR (2002) Pharmacokinetics and tissue distribution of idarubicin- loaded solid lipid nanoparticles after duodenal administration to rats. J Pharm Sci 91:1324–1333PubMedCrossRefGoogle Scholar
  200. Zeng F, Ju RJ, Li XT, Lu WL (2014) Advances in investigations on the mechanism of cancer multidrug resistance and the liposomes-based treatment strategy. J Pharm Invest 44:493–504CrossRefGoogle Scholar
  201. Zhang X, Gan Y, Gan L, Nie S, Pan W (2008a) PEGylated nanostructured lipid carriers loaded with 10- hydroxycamptothecin: an efficient carrier with enhanced anti- tumour effects against lung cancer. J Pharm Pharmacol 60:1077–1087PubMedCrossRefGoogle Scholar
  202. Zhang XG, Miao J, Dai YQ, Du YZ, Yuan H, Hu FQ (2008b) Reversal activity of nanostructured lipid carriers loading cytotoxic drug in multi-drug resistant cancer cells. Int J Pharm 361:239–244PubMedCrossRefGoogle Scholar
  203. Zhang J, Jin W, Wang X, Wang J, Zhang X, Zhang Q (2010) A novel octreotide modified lipid vesicle improved the anticancer efficacy of doxorubicin in somatostatin receptor 2 positive tumor models. Mol Pharm 7:1159–1168PubMedCrossRefGoogle Scholar
  204. Zhang X, Guo S, Fan R, Yu M, Li F, Zhu C, Gan Y (2012) Dual-functional liposome for tumor targeting and overcoming multidrug resistance in hepatocellular carcinoma cells. Biomaterials 33:7103–7114PubMedCrossRefGoogle Scholar
  205. Zhang L, Wang Y, Yang Y, Liu Y, Ruan S, Zhang Q, Gao H (2015) High tumor penetration of paclitaxel loaded pH sensitive cleavable liposomes by depletion of tumor collagen I in breast cancer. ACS Appl Mater Interfaces 7:9691–9701PubMedCrossRefGoogle Scholar
  206. Zhang Q, Deng C, Fu Y, Sun X, Gong T, Zhang Z (2016a) Repeated administration of hyaluronic acid coated liposomes with improved pharmacokinetics and reduced immune response. Mol Pharm 13:1800–1808PubMedCrossRefGoogle Scholar
  207. Zhang S, Lu C, Zhang X, Li J, Jiang H (2016b) Targeted delivery of etoposide to cancer cells by folate-modified nanostructured lipid drug delivery system. Drug Deliv 23:1838–1845PubMedCrossRefGoogle Scholar
  208. Zheng J, Wan Y, Elhissi A, Zhang Z, Sun X (2014) Targeted paclitaxel delivery to tumors using cleavable PEG-conjugated solid lipid nanoparticles. Pharm Res 31:2220–2233PubMedCrossRefGoogle Scholar
  209. Zhu L, Kate P, Torchilin VP (2012) Matrix metalloprotease 2-responsive multifunctional liposomal nanocarrier for enhanced tumor targeting. ACS Nano 6:3491–3498PubMedPubMedCentralCrossRefGoogle Scholar
  210. Zhu Y, Cheng L, Cheng L, Huang F, Hu Q, Li L, Chen D (2014) Folate and TAT peptide co-modified liposomes exhibit receptor-dependent highly efficient intracellular transport of payload in vitro and in vivo. Pharm Res 31:3289–3330PubMedCrossRefGoogle Scholar

Copyright information

© The Korean Society of Pharmaceutical Sciences and Technology 2017

Authors and Affiliations

  • Chang Hyun Kim
    • 1
  • Sang Gon Lee
    • 1
  • Myung Joo Kang
    • 2
  • Sangkil Lee
    • 3
  • Young Wook Choi
    • 1
  1. 1.College of PharmacyChung-Ang UniversitySeoulSouth Korea
  2. 2.College of PharmacyDankook UniversityCheonanSouth Korea
  3. 3.College of PharmacyKeimyung UniversityDaeguSouth Korea

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