Near-infrared-activated anticancer platinum(IV) complexes directly photooxidize biomolecules in an oxygen-independent manner
Through close collaboration, Prof. He Mingliang (Department of Biomedical Sciences, BMS) and Prof. Zhu Guangyu (Department of Chemistry, CHEM) jointly published a paper entitled as "Near-infrared-activated anticancer platinum(IV) complexes directly photooxidize biomolecules in an oxygen-independent manner" in Nature Chemistry for novel anticancer drug development. Compared with conventional chemotherapy, these photoactivatable treatments feature several unique advantages, including temporally and spatially controllable activation, an absence of cross-resistance with chemotherapeutic agents, and a minimally invasive nature. In this paper, they reported that the use of near-infrared-activated small-molecule Pt(IV) photooxidants to directly oxidize intracellular biomolecules in an oxygen-independent manner, achieving controllable and effective elimination of cancer stem cells. The Pt(IV) complexes accumulate in the endoplasmic reticulum and show low toxicity in the dark. Upon irradiation, the resultant metal-enhanced photooxidation effect causes them to robustly photooxidize survival-related biomolecules, induce intense oxidative stress, disrupt intracellular pH homeostasis and initiate nonclassical necrosis. The also confirmed that the lead photooxidant can effectively inhibit tumour growth, suppress metastasis and activate the immune system in animal models. The study validates the concept of metal-enhanced photooxidation and the subsequent chemotherapeutic applications, supporting the development of such localized photooxidants to directly damage intracellular biomolecules as a strategy for effective metal-based drugs.