Novel Ru(II) Complexes as Type-I/-II Photosensitizers for Multimodal Hypoxia-Tolerant Chemo-Photodynamic/Immune Therapy.

Photodynamic therapy (PDT) is increasingly regarded as an attractive approach for cancer treatment due to its advantages of low invasiveness, minimal side effects, and high efficiency. Here, two novel Ru(II) complexes , were designed and synthesized by coordinating phenanthroline and biquinoline ligands with Ru(II) center, and their chemo-photodynamic therapy and immunotherapy were explored. Both and exhibited significant phototoxicity against A549 and 4T1 tumor cells type-I/-II PDT. Among them, exhibited superior oxygen-independent antitumor effects (ICs = 1.50-1.76 μM) upon laser irradiation, and displayed micromolar-level chemotherapeutic activities, indicating its potential for chemo/photodynamic dual effects. Furthermore, also initiated an ICD cascade, enhancing recruitment and maturation of antigen-presenting cells, thus triggering a CD8 T cell antitumor immune response. Finally, antitumor experiments demonstrated that exhibited significant inhibition of lung and breast tumor growth, with inhibition rates of 94.6% and 97.3%, respectively. Therefore, the Ru(II) complexes we designed, as effective type-I/-II photosensitizers and potential immunoactivators, demonstrate multiple antitumor mechanisms, warranting further study.