摘要
A commercial albumin-bound paclitaxel nano-formulation has been considered a gold standard against breast cancer.However,its application still restricted unfavorable pharmacokinetics and the immunogenicity of exogenous albumin carrier.Herein,we report an albumin-bound tumor redoxresponsive paclitaxel prodrugs nano-delivery strategy.Using diverse linkages(thioether bond and disulfide bond),paclitaxel(PTX)was conjugated with an albumin-binding maleimide(MAL)functional group.These pure PTX prodrugs could self-assemble to form uniform and spherical nanoparticles(NPs)in aqueous solution without any excipients.By immediately binding to blood circulating albumin after intravenous administration,NPs are rapidly disintegrated into small prodrug/albumin nanoaggregates in vivo,facilitating PTX prodrugs accumulation in the tumor region via albumin receptormediated active targeting.The tumor redox dual-responsive drug release property of prodrugs improves the selectivity of cytotoxicity between normal and cancer cells.Moreover,disulfide bond-containing prodrug/albumin nanoaggregates exhibit long circulation time and superior antitumor efficacy in vivo.This simple and facile strategy integrates the biomimetic characteristic of albumin,tumor redox-responsive on-demand drug release,and provides new opportunities for the development of the high-efficiency antitumor nanomedicines.
基金
supported by National Natural Science Foundation of China(No.81773656 and U1608283)
Liaoning Revitalization Talents Program(No XLYC1808017,China)
Key projects of Technology bureau in Shenyang(No.18400408,China)
Key projects of Liaoning Province Department of Education(No.2017LZD03,China)
111 Project(D20029,China)
作者简介
Xinyu Lou,made equal contributions to this work;Dong Zhang,made equal contributions to this work;Corresponding authors:Mengchi Sun,Tel./fax:+862423984318,E-mail addresses:smc_1990@aliyun.com;Corresponding authors:Dongchun Liu,Tel./fax:+862423986321,E-mail addresses:liudongchun@outlook.com
