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Single-cell chemistry of photoactivatable platinum anticancer complexes

DOI: 10.1021/jacs.1c08630 DOI Help

Authors: Elizabeth M. Bolitho (University of Warwick; Diamond Light Source) , Carlos Sanchez-Cano (Center for Cooperative Research in Biomaterials (CIC biomaGUNE), Basque Research and Technology Alliance (BRTA)) , Huayun Shi (University of Warwick) , Paul D. Quinn (Diamond Light Source) , Maria Harkiolaki (Diamond Light Source) , Cinzia Imberti (University of Warwick) , Peter J. Sadler (University of Warwick)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Journal Of The American Chemical Society , VOL 8

State: Published (Approved)
Published: November 2021
Diamond Proposal Number(s): 22696 , 21505 , 25824

Open Access Open Access

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.

Journal Keywords: X-ray absorption near edge spectroscopy; Platinum; Cells; Light; Irradiation

Diamond Keywords: Prostate Cancer

Subject Areas: Chemistry, Biology and Bio-materials, Medicine


Instruments: B24-Cryo Soft X-ray Tomography , I14-Hard X-ray Nanoprobe

Added On: 24/11/2021 11:49

Documents:
jacs.1c08630.pdf

Discipline Tags:

Non-Communicable Diseases Molecular Complexes Health & Wellbeing Cancer Chemistry Drug Discovery Life Sciences & Biotech

Technical Tags:

Imaging Spectroscopy Tomography X-ray Fluorescence (XRF) X-ray Absorption Spectroscopy (XAS) X-ray Absorption Near Edge Structure (XANES) Cryo-soft X-ray Tomography (Cryo-SXT)