02555nas a2200229   4500008004100000022001400041245020200055210006900257260000800326300001400334490000700348520165500355100002302010700002502033700002502058700002102083700002602104700002402130700002702154700001702181856012702198       2021                        eng d  a2041-652000aPhotoactivatable 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 therapy0 aPhotoactivatable prodrug for simultaneous release of mertansine   cFEB  a2667-26730 v123 a<p>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.</p>
1 aTiwari, Rajeshwari1 aShinde, Prashant, S.1 aSreedharan, Sreejesh1 aDey, Anik, Kumar1 aVallis, Katherine, A.1 aMhaske, Santosh, B.1 aPramanik, Sumit, kumar1 aDas, Amitava  uhttps://library.ncl.res.in/content/photoactivatable-prodrug-simultaneous-release-mertansine-and-co-along-bodipy-derivative