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GSH-Activated NIR Fluorescent Prodrug for Podophyllotoxin Delivery.

Yajing LiuShaojia ZhuKaizhi GuZhiqian GuoXiaoyu HuangMingwei WangHesham M AminWei-Hong ZhuPing Shi
Published in: ACS applied materials & interfaces (2017)
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.
Keyphrases
  • drug release
  • drug delivery
  • cancer therapy
  • photodynamic therapy
  • fluorescence imaging
  • fluorescent probe
  • type diabetes
  • quantum dots
  • stem cells
  • endothelial cells
  • cell therapy
  • insulin resistance
  • smoking cessation