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Pure redox-sensitive paclitaxel-maleimide prodrug nanoparticles:Endogenous albumin-induced size switching and improved antitumor efficiency

摘要A commercial albumin-bound paclitaxel nano-formulation has been considered a gold stan-dard against breast cancer.However,its application still restricted unfavorable pharmacokinetics and the immunogenicity of exogenous albumin carrier.Herein,we report an albumin-bound tumor redox-responsive paclitaxel prodrugs nano-delivery strategy.Using diverse linkages(thioether bond and disul-fide 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 nanoaggre-gates in vivo,facilitating PTX prodrugs accumulation in the tumor region via albumin receptor-mediated 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 pro-drug/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 anti-tumor nanomedicines.

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作者 Xinyu Lou [1] Dong Zhang [2] Hao Ling [3] Zhonggui He [3] Jin Sun [3] Mengchi Sun [3] Dongchun Liu [1] 学术成果认领
作者单位 School of Traditional Chinese Materia Medica,Shenyang Pharmaceutical University,Shenyang 110016,China [1] Wuya College of Innovation,Shenyang Pharmaceutical University,Shenyang 110016,China;Jiangsu Hengrui Medicine Co.,Ltd.,Lianyungang Eco&Tech Development Zone,Lianyungang 222047,China [2] Wuya College of Innovation,Shenyang Pharmaceutical University,Shenyang 110016,China [3]
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发布时间 2021-11-23(万方平台首次上网日期,不代表论文的发表时间)
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