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

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 (1 O 2) (in

Metallodrugs are unique: opportunities and challenges of discovery and development

“…305 Similarly, cryo-XRT revealed signicant mitochondrial damage in photoirradiated cancer cells treated with a cyclometallated Ir III photosensitiser Ir12. 306 Cryo-XRT can be coupled to other techniques such as structured illumination microscopy (cryo-SIM) 304 or hard-XRF, which enables the direct detection of metal complexes overlaid with the 3D subcellular morphology. Notably, cryo-XRT and cryo-XRF of (near-native) cancer cells treated with a potent half-sandwich Ir III complex (Ir3) have revealed the unambiguous mitochondrial localisation of Ir (L 3 -M 5 ¼ 9.18 keV).…”

Three-dimensional imaging of mitochondrial cristae complexity using cryo-soft X-ray tomography

“…On the other hand, the use of X-ray based imaging can provide information about thick and large area biological samples and under cryogenic conditions to avoid the radiation damage, for instance the modalities of X-ptychography of vegetal tissues 18 and soft X-rays of whole cells 19 . Mitochondria has been already explored by X-ray imaging to be identified in the cellular context of wild-type single cells 19,20 , in cancer cells 21,22 and isolated from the cells aiming to unveil its internal structure 23 . However, there are no reports of X-ray imaging-based analysis focusing on extracting 3D morphological and quantitative information about the OMM and IMM organization.…”

Mito‐Bomb: Targeting Mitochondria for Cancer Therapy

“…[ 175 ] However, most of the relative studies were conducted under normal oxygen conditions, while the solid tumors were hypoxic. [ 41,176,177 ] To develop organelle‐targeted PS under hypoxic conditions, Lv et al. [ 25 ] designed and synthesized two PSs based on Ir(III) complexes: Ir‐P(ph) 3 and Ir‐alkyl ( Figure a).…”

“…What is more, Zhang et al. [ 176 ] showed that Ir[(C,N) 2 (O,O)] (C,N = 1‐phenylisoquinoline and O, O = 2,2,6,6‐tetramethyl‐3,5‐heptanedionate) complex had excellent biological activity and was considered as a promising PS for PDT. It would produce 1 O 2 and oxidize key cllular proteins (e.g., heat shock proteins) with one‐photon (blue) or two‐photon (red) light irradiation, which caused cancer cells to undergo metabolic changes (anti‐proliferation).…”

“…Moreover, a study found that, when PC‐3 cells (human prostate cancer) were treated with Ir[(C,N) 2 (O,O)] followed by cryo‐Soft X‐ray tomography under blue light irradiation at low temperature, Ir[(C,N) 2 (O,O)] would target mitochondria and change the function of mitochondria without affecting other cellular components. [ 176 ] This new insight helped to better understand the cellular action of Ir PSs. Recently, Chen and co‐workers synthesized two novel cyclometalated Ir(III) complexes, [Ir(BrQ)(L1) 2 ] (Ir‐1) and [Ir(BrQ)(L2) 2 ] (Ir‐2), by mixing the following three units: 5‐bromo‐8‐quinolinol (H‐BrQ), 2‐phenylpyridine (H‐L1) and 1‐phenylpyrazole (H‐L2).…”