Selective Photothermal Therapy Using Antioxidant Nanoparticles Encapsulating Novel Near-Infrared-Absorbing Platinum(II) Complexes

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Photothermal therapy (PTT) is a promising approach for cancer treatment that has minimal side effects. It locally heats tumors using agents that convert near-infrared (NIR) light energy into heat. We previously reported that the NIR-absorbing hydrophobic diradical-platinum(II) complex PtL₂ (L = 3,5-dibromo-1,2-diiminobenzosemiquinonato radical) can kill cancer cells through its photothermal conversion ability. In this study, we developed PtL₂-loading nanoparticles (PtL₂@RNPs) for the delivery of the complex to tumors based on the enhanced permeability and retention effect using an amphiphilic block copolymer that can scavenge reactive oxygen species. PtL₂@RNPs exhibited particle diameters of 20-30 nm, an encapsulation efficiency exceeding 90%, and loading capacities of up to 12%. Under NIR laser irradiation, PtL₂@RNPs stably generated heat with almost 100% photothermal conversion efficiency. Although the particles were not modified for cancer cell targeting, their uptake by cancer cells was approximately double that by normal cells. PtL₂@RNPs exhibited NIR absorption and effectively killed cancer cells at a low irradiation power (0.15 W). Normal cells treated with PtL₂@RNPs remained largely undamaged under identical irradiation conditions, demonstrating a cancer-cell-specific photothermal killing effect. These findings can provide insights for future basic studies on cancer cells and the development of effective cancer treatment modalities.