Rational engineering of a Schiff base-iridium(III) complex for enhanced photodynamic therapy.

Photodynamic therapy (PDT) eliminates tumors through light-activated reactive oxygen species (ROS) generation, offering a non-invasive treatment with broad anticancer activity and minimal resistance development. However, traditional organic photosensitizers (PSs) have inherent deficiencies in terms of triplet generation efficiency and the regulation of photophysical properties due to the absence of heavy atoms in their molecular structures. Herein, we developed a novel iridium(III) complex PS, Ir-NCN, which achieves highly efficient antitumor effects through molecular structure optimization by employing a benzothiazole derivative as the main ligand and incorporating a D-π-D type Schiff base auxiliary ligand, leading to a significantly enhanced singlet oxygen (1O2) quantum yield of ΦΔ = 0.39. Experimental results demonstrate that this complex efficiently generates 1O2 upon light irradiation, and in vitro studies confirm its potent cytotoxicity against HepG2 cells. In a 4T1 tumor-bearing mouse model, Ir-NCN-mediated PDT exhibited superior therapeutic efficacy compared to the cisplatin control group, with no significant toxicity observed. This study provides new insights into the development of highly efficient and low-toxicity PDT agents, demonstrating promising potential for clinical translation.