GSH-Activated NIR Fluorescent Prodrug for Podophyllotoxin Delivery

Citations Over TimeTop 10% of 2017 papers

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.

Related Papers

• → Biosynthetic relationship of aryltetralin lactone lignans to dibenzylbutyrolactone lignans(1986)58 cited
• → Synthesis and anticancer activity of podophyllotoxin derivatives with nitrogen-containing heterocycles(2023)10 cited
• → The emergence of nanocarriers in the management of diseases and disorders(2023)5 cited
• → Podophyllotoxin(2018)8 cited
• [Preliminary report of podophyllotoxin in the treatment of genital warts in China].(1991)