Abstract

The organoiridium complex Ir[(C,N)₂(O,O)] (1) where C, N = 1-phenylisoquinoline and O,O = 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.

Graphic abstract

中文翻译：

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冷冻保存的人前列腺癌细胞的 X 射线断层扫描：有机铱光敏剂的线粒体靶向。

摘要

有机铱络合物 Ir[(C,N) ₂ (O,O)] ( 1 ) 其中 C, N = 1-苯基异喹啉和 O,O = 2,2,6,6-四甲基-3,5-庚二酸酯是用于光动力疗法 (PDT) 的有前途的光敏剂。1在黑暗中对细胞无毒。然而，用单光子蓝光或双光子红光照射化合物会产生高水平的单线态氧 ( ¹ O ₂ )（在 Zhang 等人 Angew Chem Int Ed Engl 56 (47):14898-14902 https:/ /doi.org/10.1002/anie.201709082,2017)，在细胞单层和肿瘤模型中。此外，光激发1氧化关键蛋白质，导致癌细胞代谢改变，具有有效的抗增殖活性。在这里，通过冷冻软 X 射线断层扫描 (cryo-SXT) 获得的断层扫描图显示，用1处理、用蓝光照射并冷冻保存以保持它们的天然状态的人 PC3 前列腺癌细胞，表明照射会导致广泛和特异性的改变线粒体，但不改变其他细胞成分。对使用铱光敏剂在 PDT 期间对细胞产生¹ O ₂的影响的这种新见解有助于详细了解它们的细胞作用模式。

图形摘要