Preclinical evaluation demonstrates high photocytotoxicity and nuclear destruction by a platinum-iridium conjugate in cancer cells, highlighting a novel dual phototherapy strategy.
The novel hetero‐dinuclear complex trans , trans , trans ‐[Pt IV (py) 2 (N 3 ) 2 (OH)(μ‐OOCCH 2 CH 2 CONHCH 2 ‐bpyMe)Ir III (ppy) 2 ]Cl ( Pt‐Ir ), exhibits charge transfer between the acceptor photochemotherapeutic Pt(IV) ( Pt‐OH ) and donor photodynamic Ir(III) ( Ir‐NH 2 ) fragments. It is stable in the dark, but undergoes photodecomposition more rapidly than the Pt(IV) parent complex ( Pt‐OH ) to generate Pt(II) species, an azidyl radical and 1 O 2 . The Ir(III) * excited state, formed after irradiation, can oxidise NADH to NAD⋅ radicals and NAD + . Pt‐Ir is highly photocytotoxic towards cancer cells with a high photocytotoxicity index upon irradiation with blue light (465 nm, 4.8 mW/cm 2 ), even with short light‐exposure times (10–60 min). In contrast, the mononuclear Pt‐OH and Ir‐NH 2 subunits and their simple mixture are much less potent. Cellular Pt accumulation was higher for Pt‐Ir compared to Pt‐OH . Irradiation of Pt‐Ir in cancer cells damages nuclei and releases chromosomes. Synchrotron‐XRF revealed ca . 4× higher levels of intracellular platinum compared to iridium in Pt ‐ Ir treated cells under dark conditions. Luminescent Pt‐Ir distributes over the whole cell and generates ROS and 1 O 2 within 1 h of irradiation. Iridium localises strongly in small compartments, suggestive of complex cleavage and excretion via recycling vesicles (e.g. lysosomes). The combination of PDT and PACT motifs in one molecule, provides Pt‐Ir with a novel strategy for multimodal phototherapy.
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Shi et al. (2024) studied this question.
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