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Biodegradable Micelles Based on Poly(ethylene glycol)-b-polylipopeptide Copolymer: A Robust and Versatile Nanoplatform for Anticancer Drug Delivery

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机构: [1]Biomedical Polymers Laboratory, and Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou, 215123, China [2]Department of Neurosurgery, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China
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关键词: polypeptide lipopeptide micelles docetaxel drug delivery cancer therapy

摘要:
Poly(ethylene glycol)-b-polypeptide block copolymer micelles, with excellent safety, are one of the most clinically studied nanocarriers for anticancer drug delivery. Notably, self-assembled nanosystems based on hydrophobic polypeptides showing typically a low drug loading and burst drug release are limited to preclinical studies. Here, we report that poly(ethylene glycol)-b-poly(alpha-aminopalmitic acid) (PEG-b-PAPA) block copolymer could be easily prepared with tailored M-n through ring-opening polymerization of alpha-aminopalmitic acid N-carboxyanhydride (APA-NCA). Interestingly, PEG-b-PAPA copolymers exhibited superb solubility in common organic solvents (including CHCl3, CH2C6 and THF), while stable nanomicelles were formed in phosphate buffer, with a small size of 59 nm and a low critical micelle concentration of 2.38 mg/L. These polylipopeptide micelles (Lipep-Ms) allowed facile loading of a potent anticancer drug, docetaxel (DTX), likely due to the existence of a strong interaction between the lipophilic drug and polylipopeptide in the core. Notably, cRGD-peptide-functionalized Lipep-Ms (cRGD-Lipep-Ms) were also obtained with similar biophysical characteristics. The in vitro studies showed efficient cellular uptake of DTX-loaded cRGD-Lipep-Ms by B16F10 cells and fast intracellular drug release due to the enzymatic degradation of PAPA blocks in endo/lysosome, leading to a pronounced anticancer effect (IC50 = 0.15 mu g DTX equiv/mL). The in vivo therapy studies showed that DTX-cRGD-Lipep-Ms exhibited superior tumor growth inhibition of B16F10 melanoma, improved survival rate, and little side effects as compared to free DTX. These polylipopeptide micelles appear as a promising and robust nanoplatform for anticancer drug delivery.

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出版当年[2016]版:
大类 | 1 区 工程技术
小类 | 2 区 材料科学:综合 2 区 纳米科技
最新[2023]版:
大类 | 2 区 材料科学
小类 | 2 区 材料科学:综合 2 区 纳米科技
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出版当年[2015]版:
Q1 NANOSCIENCE & NANOTECHNOLOGY Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY
最新[2023]版:
Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY Q1 NANOSCIENCE & NANOTECHNOLOGY

影响因子: 最新[2023版] 最新五年平均 出版当年[2015版] 出版当年五年平均 出版前一年[2014版] 出版后一年[2016版]

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第一作者机构: [1]Biomedical Polymers Laboratory, and Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou, 215123, China
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通讯机构: [1]Biomedical Polymers Laboratory, and Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou, 215123, China
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