GSH-Activated NIR Fluorescent Prodrug for Podophyllotoxin Delivery

Yajing Liu, Shaojia Zhu, Kaizhi Gu, Zhiqian Guo, Xiaoyu Huang, Mingwei Wang, Hesham M. Amin, Weihong Zhu, Ping Shi

Research output: Contribution to journalArticlepeer-review

65 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)29496-29504
Number of pages9
JournalACS Applied Materials and Interfaces
Volume9
Issue number35
DOIs
StatePublished - Sep 6 2017
Externally publishedYes

Keywords

  • DCM-S-PPT
  • NIR fluorescent reporter
  • PPT
  • mPEG-DSPE
  • prodrug

ASJC Scopus subject areas

  • General Materials Science

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