Photoredox-Mediated Immunotherapy Utilizing Rhenium(I) Photocatalysts with Electron Donor–Acceptor–Donor Configuration
Dan Li, Guoqing Wen, Haobing Wang, Qingyan Ren, Deliang Wang, Anyi Dao, Huaiyi Huang, Pingyu Zhang
Abstract
The hypoxic environment of solid tumors significantly diminishes the therapeutic efficacy of oxygen-dependent photodynamic therapy. Developing efficient photosensitizers that operate via photoredox catalysis presents a promising strategy to overcome this challenge. Herein, we report the rational design of two rhenium(I) tricarbonyl complexes ( Re-TPO and Re-TP ) with electron donor–acceptor–donor configuration. Notably, Re-TP exhibits aggregation-induced emission properties and enhanced spin–orbit coupling compared to Re-TPO, thus exhibiting promoted photosensitizing capability. In addition to generating type I and II reactive oxygen species, the excited Re-TP facilitates the photocatalytic oxidation of NADH to NAD + and the photoreduction of pyruvic acid to lactic acid. This metabolic intervention triggers PD-L1-linked immune responses and disrupts tumor redox balance, leading to ferroptosis and immunogenic cell death. The combined ferroptosis and immunotherapy effects significantly suppress both primary and distant B16 tumors. This investigation provides a compelling model for designing efficient metal-based PSs for photoredox-mediated photoimmunotherapy against hypoxic tumors.