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Single-cell chemistry of photoactivatable platinum anticancer complexes

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Bolitho, Elizabeth, Sanchez-Cano, Carlos, Shi, Huayun, Quinn, Paul D., Harkiolaki, Maria, Imberti, Cinzia and Sadler, Peter J. (2021) Single-cell chemistry of photoactivatable platinum anticancer complexes. Journal of the American Chemical Society, 143 (48). pp. 20224-20240. doi:10.1021/jacs.1c08630 ISSN 1520-5126.

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Official URL: https://doi.org/10.1021/jacs.1c08630

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Abstract

The Pt(IV) prodrug trans, trans, trans-[Pt(pyridine)2(N3)2(OH)2] (Pt1) and its coumarin derivative trans, trans, trans-[Pt(pyridine)2(N3)2(OH)(coumarin-3-carboxylate)] (Pt2) are promising agents for photoactivated chemotherapy. These complexes are inert in the dark but release Pt(II) species and radicals upon visible light irradiation, resulting in photocytotoxicity toward cancer cells. Here, we have used synchrotron techniques to investigate the in-cell behavior of these prodrugs and visualize, for the first time, changes in cellular morphology and Pt localization upon treatment with and without light irradiation. We show that photoactivation of Pt2 induces remarkable cellular damage with extreme alterations to multiple cellular components, including formation of vacuoles, while also significantly increasing the cellular accumulation of Pt species compared to dark conditions. X-ray absorption near-edge structure (XANES) measurements in cells treated with Pt2 indicate only partial reduction of the prodrug upon irradiation, highlighting that phototoxicity in cancer cells may involve not only Pt(II) photoproducts but also photoexcited Pt(IV) species.

Item Type: Journal Article
Subjects: Q Science > QH Natural history
Q Science > QP Physiology
R Medicine > RC Internal medicine
R Medicine > RM Therapeutics. Pharmacology
T Technology > TK Electrical engineering. Electronics Nuclear engineering
Divisions: Faculty of Science, Engineering and Medicine > Science > Chemistry
SWORD Depositor: Library Publications Router
Library of Congress Subject Headings (LCSH): Irradiation , Cell metabolism, Photochemotherapy , Cancer -- Photochemotherapy, Phototherapy , Light -- Physiological effect
Journal or Publication Title: Journal of the American Chemical Society
Publisher: American Chemical Society (ACS)
ISSN: 1520-5126
Official Date: 8 December 2021
Dates:
DateEvent
8 December 2021Published
22 November 2021Available
2021Accepted
Volume: 143
Number: 48
Page Range: pp. 20224-20240
DOI: 10.1021/jacs.1c08630
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access (Creative Commons)
Date of first compliant deposit: 10 January 2022
Date of first compliant Open Access: 11 January 2022
RIOXX Funder/Project Grant:
Project/Grant IDRIOXX Funder NameFunder ID
EP/P030572/1[EPSRC] Engineering and Physical Sciences Research Councilhttp://dx.doi.org/10.13039/501100000266
209173/Z/17/ZWellcome Trusthttp://dx.doi.org/10.13039/100010269
UNSPECIFIEDAnglo Platinum (Firm)http://viaf.org/viaf/145251518
studentshipDiamond Light Sourcehttp://dx.doi.org/10.13039/100011889
studentshipUniversity of Warwickhttp://dx.doi.org/10.13039/501100000741
2019- FELL-000018-01/62/2019Guipúzcoa (Spain) Excma. Diputación Foralhttp://viaf.org/viaf/141389212
MDM-2017-0720Ministerio de Ciencia e Innovaciónhttp://dx.doi.org/10.13039/501100004837
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