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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
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 | ||||||||||||||||||||||||
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| 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 |
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| 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: |
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| 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: |
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