文献类型：期刊文献

英文题名：In Vivo and in Situ Tracking Cancer Chemotherapy by Highly Photostable NIR Fluorescent Theranostic Prodrug

作者：Wu, Xumeng[1,2];Sun, Xuanrong[3,4];Guo, Zhiqian[1,2];Tang, Jianbin[3,4];Shen, Youqing[3,4];James, Tony D.[5];Tian, He[1,2];Zhu, Weihong[1,2]

机构：[1]E China Univ Sci & Technol, Key Lab Adv Mat, Shanghai 200237, Peoples R China;[2]E China Univ Sci & Technol, Shanghai Key Lab Funct Mat Chem, Inst Fine Chem, Shanghai 200237, Peoples R China;[3]Zhejiang Univ, Ctr Bionanoengn, Minist Educ, Key Lab Biomass Chem Engn, Hangzhou 310027, Zhejiang, Peoples R China;[4]Zhejiang Univ, Dept Chem & Biol Engn, Hangzhou 310027, Zhejiang, Peoples R China;[5]Univ Bath, Dept Chem, Bath BA2 7AY, Avon, England

年份：2014

卷号：136

期号：9

起止页码：3579

外文期刊名：JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

收录：;EI(收录号：20141117456940);WOS:【SCI-EXPANDED(收录号:WOS:000332684700038)】；

基金：This work was supported by National 973 Program (2013CB733700), NSFC/China, NSFC for Distinguished Young Scholars (Grant No. 21325625), the Oriental Scholarship, National Major Scientific Technological Special Project (2012YQ15008709), SRFDP 20120074110002, Shanghai Pujiang Program (13PJD010), the Fundamental Research Funds for the Central Universities (WK1013002, WJ1114013, 222201313010), and Open Funding Project of the State Key Laboratory of Bioreactor Engineering. The Catalysis And Sensing for our Environment (CASE) network is thanked for research exchange opportunities. T.D.J. thanks ECUST for a guest professorship.

语种：英文

外文关键词：Controlled drug delivery - Chemotherapy - Nanoparticles - Oncology - Sulfur compounds - Fluorophores - Targeted drug delivery - Drug products - Diseases - Infrared devices

摘要：In vivo monitoring of the biodistribution and activation of prodrugs is urgently required. Near infrared (NIR) fluorescence-active fluorophores with excellent photostability are preferable for tracking drug release in vivo. Herein, we describe a NIR prodrug DCM-S-CPT and its polyethylene glycol-polylactic acid (PEG-PLA) loaded nanoparticles as a potent cancer therapy. We have conjugated a dicyanomethylene-4H-pyran derivative as the NIR fluorophore with camptothecin (CPT) as the anticancer drug using a disulfide linker. In vitro experiments verify that the high intracellular glutathione (GSH) concentrations in tumor cells cause cleavage of the disulfide linker, resulting in concomitantly the active drug CPT release and significant NIR fluorescence turn-on with large Stokes shift (200 nm). The NIR fluorescence of DCM-S-CPT at 665 nm with fast response to GSH can act as a direct off-on signal reporter for the GSH-activatable prodrug. Particularly, DCM-S-CPT possesses much better photostability than ICG, which is highly desirable for in situ fluorescence-tracking of cancer chemotherapy. DCM-S-CPT has been successfully utilized for in vivo and in situ tracking of drug release and cancer therapeutic efficacy in living animals by NIR fluorescence. DCM-S-CPT exhibits excellent tumor-activatable performance when intravenously injected into tumor-bearing nude mice, as well as specific cancer therapy with few side effects. DCM-S-CPT loaded in PEG-PLA nanoparticles shows even higher antitumor activity than free CPT, and is also retained longer in the plasma. The tumor-targeting ability and the specific drug release in tumors make DCM-S-CPT as a promising prodrug, providing significant advances toward deeper understanding and exploration of theranostic drug-delivery systems.