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

Abstract 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 T 1 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.