Near-infrared absorbing Ru(ii) complexes act as immunoprotective photodynamic therapy (PDT) agents against aggressive melanoma.

摘要: Mounting evidence over the past 20 years suggests that photodynamic therapy (PDT), an anticancer modality known mostly as a local treatment, has capacity to invoke systemic antitumor immune response, leading protection against tumor recurrence. For aggressive cancers such melanoma, where chemotherapy and radiotherapy are ineffective, immunomodulating PDT adjuvant surgery is of interest. Towards development specialized photosensitizers (PSs) for treating pigmented melanomas, nine new near-infrared (NIR) absorbing PSs based on Ru(ii) tris-heteroleptic scaffold [Ru(NNN)(NN)(L)]Cl n , were explored. Compounds 2, 6, 9 exhibited high potency toward melanoma cells, with visible EC50 values low 0.292-0.602 μM PIs 156-360. Single-micromolar phototoxicity was obtained NIR-light (733 nm) up 71. The common feature these lead NIR accessible low-energy triplet intraligand (3IL) excited state singlet oxygen (1O2) quantum yields (69-93%), which only possible when photosensitizing 3IL states lower in energy than lowest metal-to-ligand charge transfer (3MLCT) typically govern polypyridyl photophysics. treatment 2 elicited pro-inflammatory response alongside immunogenic cell death mouse B16F10 cells proved safe vivo administration (maximum tolerated dose = 50 mg kg-1). Female male mice vaccinated PDT-treated challenged live 80 55% from growth, respectively, significantly improved survival excellent hazard ratios ≤0.2.