文献类型：期刊文献

英文题名：GSH-Activated NIR Fluorescent Prodrug for Podophyllotoxin Delivery

作者：Liu, Yajing[1,2];Zhu, Shaojia[1,2];Gu, Kaizhi[1,2];Guo, Zhiqian[1,2];Huang, Xiaoyu[3];Wang, Mingwei[4];Amin, Hesham M.[5];Zhu, Weihong[1,2];Shi, Ping[1,2]

机构：[1]East China Univ Sci & Technol, Key Lab Adv Mat, State Key Lab Bioreactor Engn, 130 Meilong Rd, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, Inst Fine Chem, 130 Meilong Rd, Shanghai 200237, Peoples R China;[3]Chinese Acad Sci, Shanghai Inst Organ Chem, Key Lab Synthet & Self Assembly Chem Organ Funct, 345 Lingling Rd, Shanghai 200032, Peoples R China;[4]Fudan Univ, Shanghai Canc Ctr, 270 Dongan Rd, Shanghai 200032, Peoples R China;[5]Univ Texas MD Anderson Canc Ctr, Dept Hematopathol, 1515 Holcombe Blvd, Houston, TX 77030 USA

年份：2017

卷号：9

期号：35

起止页码：29496

外文期刊名：ACS APPLIED MATERIALS & INTERFACES

收录：;EI(收录号：20173704145713);WOS:【SCI-EXPANDED(收录号:WOS:000410597500013)】；

基金：We are grateful to Dawn Chalaire for outstanding assistance with the preparation of this paper. This work was supported by grants from Shanghai Scientific and Technological Innovation Project (14520720700), National Key Research and Development Program (2016YFA0200300), NSFC for Creative Research Groups (21421004), Distinguished Young Scholars (21325625), Key Project (21636002), Fundamental Research Funds for the Central Universities (222201313010, WJ1416005 and WJ1315025), and the Scientific Committee of Shanghai (14ZR1409700 and 15XD1501400).

语种：英文

外文关键词：PPT; prodrug; NIR fluorescent reporter; DCM-S-PPT; mPEG-DSPE

摘要：Theranostic prodrug therapy enables the targeted delivery of anticancer drugs with minimized adverse effects and real-time in situ monitoring of activation of the prodrugs. In this work, we report the synthesis and biological assessment of the near-infrared (NIR) prodrug DCM-S-PPT and its amphiphilic copolymer (mPEG-DSPE)-encapsulated nanoparticles. DCM-S-PPT is composed of podophyllotoxin (PPT) as the anticancer moiety and a dicyanomethylene-4H-pyran (DCM) derivative as the NIR fluorescent reporter, which are linked by a thiol-specific cleavable disulfide bond. In vitro experiments indicated that DCM-S-PPT has low cytotoxicity and that glutathione (GSH) can activate DCM-S-PPT resulting in PPT release and a concomitant significant enhancement in NIR fluorescence at 665 nm. After being intravenously injected into tumor-bearing nude mice, DCM-S-PPT exhibited excellent tumor-activated performance. Furthermore, we have demonstrated that mPEG-DSPE as a nanocarrier loaded with DCM-S-PPT (mPEG-DSPE/DCM-S-PPT) showed even greater tumor-targeting performance than DCM-S-PPT on account of the enhanced permeability and retention effect. Its tumor-targeting ability and specific drug release in tumors make DCM-S-PPT a promising prodrug that could provide a significant strategy for theranostic drug delivery systems.