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Synthesis and evaluation of a paclitaxel-binding polymeric micelle for efficient breast cancer therapy

Science China(Life Sciences) 2018年第4期61卷 436-447页

作者： Jiajia Xiang Bihan Wu Zhuxian Zhou Shiqi Hu Ying Piao Quan Zhou Guowei Wang Jianbin Tang Xiangrui Liu Youqing Shen Key Laboratory of Biomass Chemical Engineering of Ministry of Education Center for Bionanoengineering and College of Chemical and Biological Engineering Zhejiang University

Paclitaxel(PTX) is one of the most effective anticancer drugs for the treatment of various solid tumors, but its clinical use is limited by its poor solubility, low bioavailability, and severe systemic toxicity. Encapsulation of PTX in polymeric nanoparticles is used to overcome these problems but these micelles still need improvements in stability, pharmacokinetics, therapeutic efficacy, and safety profiles. In this study, we demonstrate a facile fabrication of a stable PTX-binding micelle made from poly(ethylene glycol)-block-dendritic polylysine, whose primary amines were reacted with phenethyl isothiocyanate(PEITC), a hydrophobic anticancer agent under clinical study. The amphiphilic conjugate(PEG-Gx-PEITC; Gx, the generation of the polylysine dendron) formed well-defined micelles whose core was composed of phenyl groups and thiourea groups binding PTX via π-π stacking and hydrogen bonding. Compared with the PTX-loaded poly(ethylene glycol)-block-poly(D,L-lactide)(PEGPDLLA/PTX) micelles in clinical use, PTX-loaded PEG-Gx-PEITC third-generation(PEG-G3-PEITC/PTX) micelles showed slowed blood clearance, enhanced tumor accumulation, and thus much improved in vivo therapeutic efficacy in both subcutaneous and orthotopic human breast cancer xenografts. Therefore, PEG-G3-PEITC is a promising drug delivery system for PTX in the treatment of breast cancer.

关键词： paclitaxel delivery paclitaxel-binding phenethyl isothiocyanate dendritic polylysine polymeric micelles cancer drugdelivery enhanced stability prolonged blood circulation

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