Open Access
Chemical Science, volume 12, issue 7, pages 2667-2673
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 Rajeshwari
1, 2
,
Shinde Prashant S
3
,
Sreedharan Sreejesh
4
,
Dey Anik Kumar
1, 2
,
VALLIS K. A.
4
,
Mhaske Santosh B
2, 3
,
Pramanik Sumit Kumar
1, 2
,
Das Amitava
5
2
Academy of Scientific and innovative Research (AcSIR), Ghaziabad 201002, India
|
Publication type: Journal Article
Publication date: 2021-01-01
Journal:
Chemical Science
Quartile SCImago
Q1
Quartile WOS
Q1
Impact factor: 8.4
ISSN: 20416520, 20416539
PubMed ID:
34164035
General Chemistry
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.
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- We do not take into account publications that without a DOI.
- Statistics recalculated only for publications connected to researchers, organizations and labs registered on the platform.
- Statistics recalculated weekly.
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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. 2021. Vol. 12. No. 7. pp. 2667-2673.
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Tiwari R., Shinde P. S., Sreedharan S., Dey A. K., VALLIS K. A., Mhaske S. B., Pramanik S. K., Das A. 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. 2021. Vol. 12. No. 7. pp. 2667-2673.
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TY - JOUR
DO - 10.1039/D0SC06270G
UR - https://doi.org/10.1039%2FD0SC06270G
TI - 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
T2 - Chemical Science
AU - Tiwari, Rajeshwari
AU - Shinde, Prashant S
AU - Sreedharan, Sreejesh
AU - Dey, Anik Kumar
AU - VALLIS, K. A.
AU - Mhaske, Santosh B
AU - Pramanik, Sumit Kumar
AU - Das, Amitava
PY - 2021
DA - 2021/01/01 00:00:00
PB - Royal Society of Chemistry (RSC)
SP - 2667-2673
IS - 7
VL - 12
PMID - 34164035
SN - 2041-6520
SN - 2041-6539
ER -
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@article{2021_Tiwari,
author = {Rajeshwari Tiwari and Prashant S Shinde and Sreejesh Sreedharan and Anik Kumar Dey and K. A. VALLIS and Santosh B Mhaske and Sumit Kumar Pramanik and Amitava Das},
title = {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},
journal = {Chemical Science},
year = {2021},
volume = {12},
publisher = {Royal Society of Chemistry (RSC)},
month = {jan},
url = {https://doi.org/10.1039%2FD0SC06270G},
number = {7},
pages = {2667--2673},
doi = {10.1039/D0SC06270G}
}
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MLA
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Tiwari, Rajeshwari, 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, Jan. 2021, pp. 2667-2673. https://doi.org/10.1039%2FD0SC06270G.