Journal
POLYMER
Volume 100, Issue -, Pages 45-55Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.polymer.2016.08.012
Keywords
Biomimetic; Polypeptide; Polymeric micelles; Drug delivery; Cancer therapy
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Funding
- National Natural Science Foundation of China [51403131, 81571794, 31271020]
- Programme of Introducing Talents of Discipline to Universities [B16033]
- Sichuan Province Science and Technology Support Program [2015SZ0122]
- China Postdoctoral Science Foundation Funded Project [2015M570783]
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Polymeric nanoscale drug carrier systems are of particular interest for tumor therapy, offering significant advantages of improved targeting and efficacy. Herein, a well-defined polymeric micelle as drug carrier system is demonstrated with the functions of polypeptide based biodegradability and zwitterionic polyphosphorylcholine based biocompatibility. The polymeric micelles was self-assembled from amphiphilic poly(gamma-benzyl-L-glutamate)-block-poly(2-methacryloyloxyethyl phosphorylcholine) (PBLG-b-PMPC) diblock copolymers, with biodegradable PBLG as hydrophobic core and biomimetic PMPC as hydrophilic shell. Anticancer drugs, doxorubicin (DOX), could be encapsulated into the micelle core via the hydrophobic interaction with the polypeptide blocks, resulting in a 70 nm drug carrier with very narrow size distribution. In vitro cellular uptake and cytotoxicity studies demonstrated DOX-loaded PBLG-b-PMPC micelles were taken up by breast cancer cells via endocytosis, with slightly slower intracellular release and lower cytotoxicity compared with free DOX. However, in mice models of breast cancer, these drug-loaded micelles showed higher selectively accumulation in tumor due to the enhanced permeability and retention (EPR) effect than free drugs, leading to enhanced therapeutic efficacy, reduced systemic toxicity and increased apoptosis in tumor tissues. The in vivo results indicated this biomimetic polymeric micelle could be used as a promising strategy for systemic cancer treatment. (C) 2016 Elsevier Ltd. All rights reserved.
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