<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Tiwari, Rajeshwari</style></author><author><style face="normal" font="default" size="100%">Shinde, Prashant S.</style></author><author><style face="normal" font="default" size="100%">Sreedharan, Sreejesh</style></author><author><style face="normal" font="default" size="100%">Dey, Anik Kumar</style></author><author><style face="normal" font="default" size="100%">Vallis, Katherine A.</style></author><author><style face="normal" font="default" size="100%">Mhaske, Santosh B.</style></author><author><style face="normal" font="default" size="100%">Pramanik, Sumit kumar</style></author><author><style face="normal" font="default" size="100%">Das, Amitava</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Photoactivatable prodrug for simultaneous release of mertansine and CO along with a BODIPY derivative as a luminescent marker in mitochondria: a proof of concept for NIR image-guided cancer therapy</style></title><secondary-title><style face="normal" font="default" size="100%">Chemical Science</style></secondary-title></titles><dates><year><style  face="normal" font="default" size="100%">2021</style></year><pub-dates><date><style  face="normal" font="default" size="100%">FEB</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">12</style></volume><pages><style face="normal" font="default" size="100%">2667-2673</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Controlled and efficient activation is the crucial aspect of designing an effective prodrug. Herein we demonstrate a proof of concept for a light activatable prodrug with desired organelle specificity. Mertansine, a benzoansamacrolide, is an efficient microtubule-targeting compound that binds at or near the vinblastine-binding site in the mitochondrial region to induce mitotic arrest and cell death through apoptosis. Despite its efficacy even in the nanomolar level, this has failed in stage 2 of human clinical trials owing to the lack of drug specificity and the deleterious systemic toxicity. To get around this problem, a recent trend is to develop an antibody-conjugatable maytansinoid with improved tumor/organelle-specificity and lesser systematic toxicity. Endogenous CO is recognized as a regulator of cellular function and for its obligatory role in cell apoptosis. CO blocks the proliferation of cancer cells and effector T cells, and the primary target is reported to be the mitochondria. We report herein a new mitochondria-specific prodrug conjugate (Pro-DC) that undergoes a photocleavage reaction on irradiation with a 400 nm source (1.0 mW cm(-2)) to induce a simultaneous release of the therapeutic components mertansine and CO along with a BODIPY derivative (BODIPY(PPH3)(2)) as a luminescent marker in the mitochondrial matrix. The efficacy of the process is demonstrated using MCF-7 cells and could effectively be visualized by probing the intracellular luminescence of BODIPY(PPH3)(2). This provides a proof-of-concept for designing a prodrug for image-guided combination therapy for mainstream treatment of cancer.&lt;/p&gt;
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