%0 Journal Article
%T Self-assembly of a ruthenium-based cGAS-STING photoactivator for carrier-free cancer immunotherapy.
%A Ling YY
%A Li ZY
%A Mu X
%A Kong YJ
%A Hao L
%A Wang WJ
%A Shen QH
%A Zhang YB
%A Tan CP
%J Eur J Med Chem
%V 275
%N 0
%D 2024 Jun 28
%M 38950489
%F 7.088
%R 10.1016/j.ejmech.2024.116638
%X The cGAS (cyclic GMP-AMP synthase)-STING (stimulator of interferon genes) pathway promotes antitumor immune responses by sensing cytosolic DNA fragments leaked from nucleus and mitochondria. Herein, we designed a highly charged ruthenium photosensitizer (Ru1) with a β-carboline alkaloid derivative as the ligand for photo-activating of the cGAS-STING pathway. Due to the formation of multiple non-covalent intermolecular interactions, Ru1 can self-assemble into carrier-free nanoparticles (NPs). By incorporating the triphenylphosphine substituents, Ru1 can target and photo-damage mitochondrial DNA (mtDNA) to cause the cytoplasmic DNA leakage to activate the cGAS-STING pathway. Finally, Ru1 NPs show potent antitumor effects and elicit intense immune responses in vivo. In conclusion, we report the first self-assembling mtDNA-targeted photosensitizer, which can effectively activate the cGAS-STING pathway, thus providing innovations for the design of new photo-immunotherapeutic agents.