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X-ray tomography of cryopreserved human prostate cancer cells: mitochondrial targeting by an organoiridium photosensitiser

DOI: 10.1007/s00775-020-01761-8 DOI Help

Authors: Elizabeth M. Bolitho (University of Warwick) , Carlos Sanchez-cano (University of Warwick; Center for Cooperative Research in Biomaterials (CIC biomaGUNE)) , Huaiyi Huang (University of Warwick) , Ian Hands-portman (University of Warwick) , Matthew Spink (Diamond Light Source) , Paul D. Quinn (Diamond Light Source) , Maria Harkiolaki (Diamond Light Source) , Peter J. Sadler (University of Warwick)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Jbic Journal Of Biological Inorganic Chemistry , VOL 56

State: Published (Approved)
Published: March 2020
Diamond Proposal Number(s): 18339 , 19615

Open Access Open Access

Abstract: The organoiridium complex Ir[(C,N)2(O,O)] (1) where C, Nā€‰=ā€‰1-phenylisoquinoline and O,Oā€‰=ā€‰2,2,6,6-tetramethyl-3,5-heptanedionate is a promising photosensitiser for Photo-Dynamic Therapy (PDT). 1 is not toxic to cells in the dark. However, irradiation of the compound with one-photon blue or two-photon red light generates high levels of singlet oxygen (1O2) (in Zhang et al. Angew Chem Int Ed Engl 56 (47):14898-14902 https://doi.org/10.1002/anie.201709082,2017), both within cell monolayers and in tumour models. Moreover, photo-excited 1 oxidises key proteins, causing metabolic alterations in cancer cells with potent antiproliferative activity. Here, the tomograms obtained by cryo-Soft X-ray Tomography (cryo-SXT) of human PC3 prostate cancer cells treated with 1, irradiated with blue light, and cryopreserved to maintain them in their native state, reveal that irradiation causes extensive and specific alterations to mitochondria, but not other cellular components. Such new insights into the effect of 1O2 generation during PDT using iridium photosensitisers on cells contribute to a detailed understanding of their cellular mode of action.

Journal Keywords: Photodynamic therapy; Iridium complexes; Phosphorescence; Anticancer metallodrugs; Cryo-soft X-ray tomography; X-ray microscopy

Subject Areas: Biology and Bio-materials


Instruments: B24-Cryo Soft X-ray Tomography

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s00775-020-01761-8.pdf

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