Surface modification of lipid-based nanocarriers for cancer cell-specific drug targeting
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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.
KeywordsLipid-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.
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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.
- 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
- 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
- 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
- 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
- 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
- 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
- Necas J, Bartosikova L, Brauner P, Kolar J (2008) Hyaluronic acid (hyaluronan): a review. Vet Med (Praha) 53 :397–411Google Scholar
- 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
- 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
- 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
- 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