文献类型：期刊文献

英文题名：Gradient Redox-Responsive and Two-Stage Rocket-Mimetic Drug Delivery System for Improved Tumor Accumulation and Safe Chemotherapy

作者：Jia, Xiaobo[1];He, Jianping[1];Shen, Luying[1];Chen, Jianzhuang[1];Wei, Zhenyang[1];Qin, Xing[1];Niu, Dechao[1];Li, Yongsheng[1];Shi, Jianlin[1,2]

机构：[1]East China Univ Sci & Technol, Lab Low Dimens Mat Chem, Shanghai Engn Res Ctr Hierarch Nanomat, Sch Mat Sci & Engn,Key Lab Ultrafine Mat,Minist E, Shanghai 200237, Peoples R China;[2]Chinese Acad Sci, Shanghai Inst Ceram, State Key Lab High Performance Ceram & Superfine, Shanghai 200050, Peoples R China

年份：2019

卷号：19

期号：12

起止页码：8690

外文期刊名：NANO LETTERS

收录：;EI(收录号：20194807758930);WOS:【SCI-EXPANDED(收录号:WOS:000502687500043)】；

基金：This work was financially supported by the National Key Research and Development Program of China (Grant Nos. 2018YFC1105702 and 2016YFA0203700), The National Natural Science Foundation of China for Innovative Research Groups (Grant No. 51621002), NSFC (Grant Nos. 51572083 and 51972112), Program of Shanghai Academic/Technology Research Leader (Grant 18XD1401400), Basic Research Program of Shanghai (Grant 17JC1404702), Leading Talents in Shanghai in 2018, The Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning, The 111 Project (Grant B14018), and the Fundamental Research Funds for Central Universities (Grant 222201718002). All animal experiments were performed in compliance with the Guidelines for the Care and Use of Research Animals established by the East China University of Science and Technology Animal Studies Committee.

语种：英文

外文关键词：Gradient redox-responsiveness; two-stage rocket mimics; tumor accumulation; drug delivery; safe chemotherapy

摘要：Recent drug delivery nanosystems for cancer treatment still suffer from the poor tumor accumulation and low therapeutic efficacy due to the complex in vivo biological barriers. To resolve these problems, in this work, a novel gradient redox-responsive and two-stage rocket-mimetic drug nanocarrier is designed and constructed for improved tumor accumulation and safe chemotherapy. The nanocarrier is constructed on the basis of the disulfide-doped organosilica-micellar hybrid nanoparticles and the following dual-functional modification with disulfide-bonded polyethylene glycol (PEG) and amido-bonded polyethylenimine (PEI). First, prolonged circulation duration in the bloodstream is guaranteed due to the shielding of the outer PEG chains. Once the nanocarrier accumulates at the tumoral extracellular microenvironment with low glutathione (GSH) concentrations, the first-stage redox-responsive behavior with the separation of PEG and the exposure of PEI is triggered, leading to the improved tumor accumulation and cellular internalization. Furthermore, with their endocytosis by tumor cells, a high concentration of GSH induces the second-stage redox-responsiveness with the degradation of silsesquioxane framework and the release of the encapsulated drugs. As a result, the rocket-mimetic drug carrier displays longer circulation duration in the bloodstream, higher tumor accumulation capability, and improved antitumor efficacy (which is 2.5 times higher than that with inseparable PEG). It is envisioned that the rocket-mimetic strategy can provide new solutions for improving tumor accumulation and safety of nanocarriers in further cancer chemotherapy.