Grafted copolymer micelles with pH triggered charge reversibility for efficient doxorubicin delivery

	Grafted copolymer micelles with pH triggered charge reversibility for efficient doxorubicin delivery
	Wu, Shaohua 1,2; Zheng, Liuchun 1; Li, Chuncheng 1; Xiao, Yaonan 1; Huo, Shuaidong 2,3; Zhang, Bo 1
刊名	JOURNAL OF POLYMER SCIENCE PART A-POLYMER CHEMISTRY
	2017-06-15
卷号	55 期号:12 页码:2036-2046
关键词	Biocompatibility Charge-reversal Co-assembly Controlled Release Micelles Stimuli-sensitive Polymers
英文摘要	The instability and premature charge reversal at pH 7.4 have become the major limitations of charge-reversal delivery systems. To address this problem, graft copolymer of poly(butylene succinate)-g-cysteamine-bi-poly(ethylene glycol) (PBS-g-CS-bi-PEG, bi=benzoic imine bond) was designed and synthesized through facile thiol-ene click reaction and subsequent Schiff's base reaction. Then, PBS-g-CS-bi-PEG and carboxyl-functionalized polyester of poly(butylene succinate)-g-3-mercaptopropionic acid (PBS-g-MPA) co-assemble in aqueous solution to give PEG shell-sheddable charge-reversal micelles with sizes of 85-103 nm and low polydispersity of 0.11-0.12. Interestingly, the PBS-g-MPA/CS-bi-PEG micelles could sensitively and arbitrarily switch their surface charges between negative and positive status in response to pH fluctuation via reversible protonation and deprotonation of carboxyl and amino groups, which endows the desired stability of co-assembly micelles either during long-term storage or under physiological conditions. Doxorubicin (DOX) was loaded into PBS-g-MPA/CS-bi-PEG micelles with a high drug-loading content of 10.2% and entrapment efficiency of 68% as a result of electrostatic attraction. In vitro release studies revealed that less than 25% of DOX was released within 24 h in the environment mimicking the physiological condition, whereas up to 81% of DOX was released in 24 h under weak-acid condition resembling microenvironment in endosome/lysosome. In vitro cytotoxicity study suggested that blank PBS-g-MPA/CS-bi-PEG micelles possessed excellent biocompatibility, while DOX-loaded PBS-g-MPA/CS-bi-PEG micelles showed significant cytotoxicity with half-maximal inhibitory concentration (IC50) of 1.55-1.67 g DOX equiv/mL. This study provides a facile and effective approach for the preparation of novel charge-reversal micelles with switchable charges and excellent biocompatibility, which are highly promising to be used as safe nanocarriers for efficient intracellular drug delivery. (c) 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017, 55, 2036-2046
语种	英语
内容类型	期刊论文
源URL	[http://ir.iccas.ac.cn/handle/121111/39045]
专题	化学研究所_工程塑料实验室
作者单位	1.Chinese Acad Sci ICCAS, Beijing Natl Lab Mol Sci, Inst Chem, Key Lab Engn Plast, Beijing 100190, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 3.Chinese Acad Sci, Natl Ctr Nanosci & Technol, Key Lab Biol Effects Nanomat & Nanosafety, Beijing 100049, Peoples R China
推荐引用方式 GB/T 7714	Wu, Shaohua,Zheng, Liuchun,Li, Chuncheng,et al. Grafted copolymer micelles with pH triggered charge reversibility for efficient doxorubicin delivery[J]. JOURNAL OF POLYMER SCIENCE PART A-POLYMER CHEMISTRY,2017,55(12):2036-2046.
APA	Wu, Shaohua,Zheng, Liuchun,Li, Chuncheng,Xiao, Yaonan,Huo, Shuaidong,&Zhang, Bo.(2017).Grafted copolymer micelles with pH triggered charge reversibility for efficient doxorubicin delivery.JOURNAL OF POLYMER SCIENCE PART A-POLYMER CHEMISTRY,55(12),2036-2046.
MLA	Wu, Shaohua,et al."Grafted copolymer micelles with pH triggered charge reversibility for efficient doxorubicin delivery".JOURNAL OF POLYMER SCIENCE PART A-POLYMER CHEMISTRY 55.12(2017):2036-2046.