Authors
Qin Gong, Xiu-Qing Su, Shan Jiang, Liang He, Zheng-Yin Pan, Chen-Yang Li
Published in
Dalton transactions (Cambridge, England : 2003). Sep 16, 2026. Epub Sep 16, 2026.
Abstract
To overcome the limitations imposed by hypoxia in photodynamic therapy (PDT), we rationally designed and synthesized three carbonic anhydrase IX (CAIX)-targeted osmium(II) polypyridyl complexes (Os1-Os3) by conjugating a benzenesulfonamide CAIX inhibitor to the photosensitizer core. Among them, Os3 exhibited excellent photophysical properties and efficient singlet oxygen generation. This complex showed remarkable selectivity for CAIX-overexpressing MDA-MB-231 cancer cells, with very low dark toxicity (IC50 > 100 μM) and outstanding phototoxicity (IC50 = 2.2 μM, phototoxicity index = 45) upon red light irradiation (633 nm, 15 mW cm-2). Mechanistic studies revealed that upon illumination at 633 nm (15 mW cm-2), Os3 induced the generation of reactive oxygen species (ROS), which subsequently led to a decrease in mitochondrial membrane potential and reduced ATP production. Further investigations showed that Os3-mediated PDT triggered upregulation of the GSDMD-N protein, increased malondialdehyde (MDA) levels, and downregulation of GPX4 protein expression. Collectively, these results indicate that Os3-mediated PDT exerts its anticancer effects by inducing pyroptosis, and ferroptosis. In vivo, Os3-PDT significantly suppressed the growth of 4T1 tumors, achieving an inhibition rate of 58.7%. Os3 represents a CAIX-targeted osmium(II) photosensitizer that combats tumors by inducing multimodal cell death and remodeling the tumor microenvironment.
PMID:
42747048
Bibliographic data and abstract were imported from PubMed on 16 Sep 2026.
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