环金属铱(III)配合物在抗肿瘤光动力疗法 (PDT) 领域中具有重要意义，无论是作为单个分子还是与纳米材料结合存在。然而，关于它们的分子结构与 PDT 效果之间关系的综合研究仍待展开。我们预计二光子激发的 PDT 的影响因素将进一步增加，尤其是与复杂的非线性光学性质相关。目前，对这一主题的综合研究还不足，并且很少找到明显的模式。在本研究中，通过系统调整结构，在一个包含4 × 3种环金属铱(III)配合物组合库中发现，亚硝基取代的苯肟基苯乙烯基团和含有YQ2的1-苯基异喹啉配体是最有效的红外二光子可激发光敏剂。YQ2可以通过能量依赖的和空泡介导的途径进入细胞，与线粒体特异结合，在808 nm的激光照射下产生1O2，激活半胱氨酸蛋白酶，引起细胞凋亡。体外实验中，基于这些功能，YQ2在恶性黑色素瘤(>885)和非小细胞肺癌(>1234)中显示了显著的光治疗指数，并对人正常肝脏和肾脏细胞的损伤最小。在体内抗肿瘤光治疗中，YQ2能够令肿瘤生长抑制达到85％，并且能够在小鼠体内以约43小时的半衰期被排除。该研究有望对极其有效治疗大型、深度定位的实体肿瘤的光治疗药物的开发以及对基于铱(III)的光敏剂在PDT中的结构-活性关系的理解做出重要贡献。

Cyclometalated iridium(III) complexes are of significant importance in the field of antitumor photodynamic therapy (PDT), whether they exist as single molecules or are incorporated into nanomaterials. Nevertheless, a comprehensive examination of the relationship between their molecular structure and PDT effectiveness remains awaited. The influencing factors of two-photon excited PDT can be anticipated to be further multiplied, particularly in relation to intricate nonlinear optical properties. At present, a comprehensive body of research on this topic is lacking, and few discernible patterns have been identified. In this study, through systematic structure regulation, the nitro-substituted styryl group and 1-phenylisoquinoline ligand containing YQ2 was found to be the most potent infrared two-photon excitable photosensitizer in a 4 × 3 combination library of cyclometalated Ir(III) complexes. YQ2 could enter cells via an energy-dependent and caveolae-mediated pathway, bind specifically to mitochondria, produce 1O2 in response to 808 nm LPL irradiation, activate caspases, and induce apoptosis. In vitro, YQ2 displayed a remarkable phototherapy index for both malignant melanoma (>885) and non-small-cell lung cancer (>1234) based on these functions and was minimally deleterious to human normal liver and kidney cells. In in vivo antitumor phototherapy, YQ2 inhibited tumor growth by an impressive 85% and could be eliminated from the bodies of mice with a half-life as short as 43 h. This study has the potential to contribute significantly to the development of phototherapeutic drugs that are extremely effective in treating large, profoundly located solid tumors as well as the understanding of the structure-activity relationship of Ir(III)-based PSs in PDT.