GSH-Activated NIR Fluorescent Prodrug for Podophyllotoxin Delivery

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.

Integration detection of mercury(ii) and GSH with a fluorescent “on-off-on” switch sensor based on nitrogen, sulfur co-doped carbon dots

“…Especially, it is very important to monitor the level of GSH in living cells considering the high GSH concentration in cancer cells. 29,30 To monitor Hg 2+ ions 31,32 and GSH, 33,34 numerous analytical methods have been developed, including AAS, 35 electrochemical, 36 electrophoresis, 37 HPLC, 38 mass spectrometry, 39 and etc. 40 However, most of them are laborious, intricate, and in need of professional operating and expensive instruments.…”

A mitochondria targetable near-infrared fluorescence probe for glutathione visual biological detection

“…[8][9][10][11] Compared with the traditional detection methods, uorescent probes afford a variety of testing advantages such as real-time spatial and in situ imaging, high sensitivity, non-invasiveness, and low damage for biosamples. 12,13 In recent years, some mediocre designs of uorescent probes for testing GSH mostly imitate the antiquated mechanism such as Michael addition, [14][15][16][17] nucleophilic substitution, [18][19][20][21][22][23] and disulde or Se-Se bond break, [24][25][26][27][28][29] etc. 30,31 However, most of them have the disadvantages of slow response time or poor selectivity, and these problems remain a challenge.…”

A fluorescence and photoactivity dual-activatable prodrug with self-synergistic magnification of the anticancer effect

“…The HCA-SS-HCPT NPs are almost non-fluorescent and hardly generate ROS under light irradiation in aqueous environments. After thiol (e.g., glutathione (GSH), in high concentrations within many cancer cells) [31][32][33][34] responsiveness with cleavage of the disulfide bond, followed by release of intact HCPT and HCA (Scheme 2), the fluorescence and ROS generation ability of the AIEgen are restored, which can not only track the co-delivered HCPT, but also more importantly, serve as a non-toxic pro-oxidant by producing ROS to synergistically amplify the anticancer effect of HCPT by virtue of oxidation therapy. Noteworthily, by optimizing the light irradiation condition, the thiol-activated HCA can only generate a small amount of ROS, which is not high enough to kill cancer cells, but just provides an intracellular oxidative environment for oxidation therapy.…”