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

Tiwari, R; Shinde, PS; Sreedharan, S; Dey, AK; Vallis, KA; Mhaske, SB; Pramanik, SK; Das, A

Journal article

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

Abstract:: 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.

Publication status:: Published

Peer review status:: Peer reviewed

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APA Style

Tiwari, R., Shinde, P. S., Sreedharan, S., Dey, A. K., Vallis, K. A., Mhaske, S. B., Pramanik, S. K., & Das, A. (2020). 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. Chemical Science, 12(7), 2667–2673.

MLA Style

Tiwari, R., et al. “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.” Chemical Science, vol. 12, no. 7, Royal Society of Chemistry, 2020, pp. 2667–73.

Chicago Style

Tiwari, R, PS Shinde, S Sreedharan, AK Dey, KA Vallis, SB Mhaske, SK Pramanik, and A Das. 2020. “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.” Chemical Science 12 (7): 2667–73.
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