Cyclometalating Ligand Affords NIR Absorption in Ruthenium Complexes for Type‐I Photodynamic Therapy

The development of NIR photosensitizers (PSs) based on Ru complexes with Type-I process holds substantial promise for photodynamic therapy (PDT) of cancer, though this breakthrough remains unrealized to date. Herein, a pair of cyclometalated Ru enantiomers, [Λ/Δ-Ru-dqpy-TPABP]Cl (dqpy: 2,6-di(quinolin-2-yl)pyridine; TPABP: 4-(4-(pyridine-2-yl)-2,1,3-benzothiadiazol-7-yl)triphenylamine) (Λ/Δ-Ru-TPABP), were synthesized and evaluated. These complexes exhibit strong Ru(d) and TPABP(π) → dqpy(π*) charge transfer ((metal and ligand)-ligand charge transfer; ML-LCT) absorption at ∼640 nm, with an extended absorption tail reaching up to 800 nm. Moreover, the TPABP ligand, with its strong electron-rich capacity, contributes to T₁ formation, which increases the electron transfer possibility in the triplet state and promotes Type-I PDT, making it highly effective for killing cancer cells under hypoxic conditions. Further encapsulating Λ/Δ-Ru-TPABP into polymeric nanoparticles results in high tumor inhibition efficiency (>85%) and causes a strong tumoricidal effect and inhibits lung metastasis of breast tumors under 700 nm light irradiation, thus offering a new strategy for developing NIR Ru complexes for anticancer treatment through the design of cyclometalating ligand.