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Biodegradable Polymersomes with An Ionizable Membrane: Facile Preparation, Superior Protein Loading, And Endosomal pH-Responsive Protein Release
作者:S.K. Li, F.H. Meng, Z.J. Wang, Y.N. Zhong, M. Zheng, H.Y. Liu, and Z.Y. Zhong*
關(guān)鍵字:Biodegradable; Polymersomes; Protein delivery; Ionizable membrane; pH-sensitive; Cancer therapy
論文來(lái)源:期刊
具體來(lái)源:Eur. J. Pharm. Biopharm. 2012, 82, 103-111
發(fā)表時(shí)間:2012年

Novel biodegradable polymersomes containing an ionizable membrane were developed for efficient loading and rapid intracellular release of proteins. The polymersomes were prepared from poly(ethylene glycol)-b-poly(trimethylene carbonate) (PEG–PTMC) block copolymer derivatives containing acrylate, carboxylic acid, and amine groups along PTMC block, which are denoted as PEG–PTMC(AC), PEG–PTMC(COOH), and PEG–PTMC(NH2), respectively. Notably, nano-sized polymersomes (95.1–111.6 nm) were formed by directly dispersing these copolymers in phosphate buffer at room temperature. Both FITC-labeled bovine serum albumin (FITC-BSA) and cytochrome C (FITC-CC) were readily loaded into PEG–PTMC(COOH) and PEG–PTMC(NH2) polymersomes with remarkably high loading levels. Interestingly, in vitro release studies showed that PEG–PTMC(COOH) and PEG–PTMC(NH2) polymersomes had pH-responsive protein release behaviors in which significantly faster protein release was observed at endosomal pH than at physiological pH. MTT assays indicated that these polymersomes had low cytotoxicity. Furthermore, confocal laser scanning microscope (CLSM) observations revealed that FITC-CC loaded polymersomes efficiently delivered proteins into MCF-7 cells following 24 h incubation. Importantly, flow cytometry showed that CC-loaded polymersomes induced markedly enhanced apoptosis in MCF-7 cells as compared to free CC. These novel membrane ionizable biodegradable polymersomes have appeared as highly promising nanocarriers for efficient intracellular protein delivery.

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