文献类型：期刊文献

英文题名：Dual Intratumoral Redox/Enzyme-Responsive NO-Releasing Nanomedicine for the Specific, High-Efficacy, and Low-Toxic Cancer Therapy

作者：Jia, Xiaobo[1];Zhang, Yihua[2];Zou, Yu[2];Wang, Yao[1];Niu, Dechao[1];He, Qianjun[3];Huang, Zhangjian[2];Zhu, Weihong[4,5];Tian, He[4,5];Shi, Jianlin[1];Li, Yongsheng[1]

机构：[1]East China Univ Sci & Technol, Sch Mat Sci & Engn, Key Lab Ultrafine Mat, Lab Low Dimens Mat Chem,Minist Educ, Shanghai 200237, Peoples R China;[2]China Pharmaceut Univ, Jiangsu Key Lab Drug Discovery Metab Dis, State Key Lab Nat Med, Nanjing 210009, Jiangsu, Peoples R China;[3]Shenzhen Univ, Hlth Sci Ctr, Sch Biomed Engn, Guangdong Key Lab Biomed Measurements & Ultrasoun, Shenzhen 518060, Peoples R China;[4]East China Univ Sci & Technol, Key Lab Adv Mat, Shanghai Key Lab Funct Mat Chem, Shanghai 200237, Peoples R China;[5]East China Univ Sci & Technol, Inst Fine Chem, Shanghai 200237, Peoples R China

年份：2018

卷号：30

期号：30

外文期刊名：ADVANCED MATERIALS

收录：;EI(收录号：20183005610903);WOS:【SCI-EXPANDED(收录号:WOS:000439737700001)】；

基金：X.J. and Y.Z. contributed equally to this work. This work was financially supported by the National Natural Science Foundation of China for Innovative Research Groups (No. 51621002); the National Key Research and Development Program of China (Grant No. 2016YFA0203700); NSFC (Grant No 51572083, 51461165202 and 51472085); Program of Shanghai Academic/Technology Research Leader (18XD1401400); Basic Research Program of Shanghai (17JC1404702); the Shanghai Rising-Star Program (16QA1401300); the 111 project (B14018); and The Fundamental Research Funds for Central Universities (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：dual-responsiveness; nitric oxide; prodrug delivery; safe treatment; tumor therapy

摘要：Chemotherapy suffers numbers of limitations including poor drug solubility, nonspecific biodistribution, and inevitable adverse effects on normal tissues. Tumor-targeted delivery and intratumoral stimuli-responsive release of drugs by nanomedicines are considered to be highly promising in solving these problems. Compared with traditional chemotherapeutic drugs, high concentration of nitric oxide (NO) exhibits unique anticancer effects. The development of tumor-targeting and intratumoral microenvironment-responsive NO-releasing nanomedicines is highly desired. Here a novel kind of organic-inorganic composite nanomedicine (QM-NPQ@PDHNs) is presented by encapsulating a glutathione S-transferases (GST)-responsive drug O-2-(2,4-dinitro-5-{[2-(-d-galactopyranosyl olean-12-en-28-oate-3-yl)-oxy-2-oxoethyl] piperazine-1-yl} phenyl) 1-(methylethanolamino)diazen-1-ium-1,2-dilate (NPQ) as NO donor and an aggregation-induced-emission (AIE) red fluorogen QM-2 into the cores of the hybrid nanomicelles (PEGylated disulfide-doped hybrid nanocarriers (PDHNs)) with glutathione (GSH)-responsive shells. The QM-NPQ@PDHN nanomedicine is able to respond to the intratumoral over-expressed GSH and GST, resulting in the responsive biodegradation of the protective organosilica shell and NPQ release, and subsequent NO release within the tumor, respectively, and thus normal organs remain unaffected. This work demonstrates a paradigm of dual intratumoral redox/enzyme-responsive NO-release nanomedicine for tumor-specific and high-efficacy cancer therapy.