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Self-assembly of a ruthenium-based cGAS-STING photoactivator for carrier-free cancer immunotherapy.
Ling, Yu-Yi; Li, Zhi-Yuan; Mu, Xia; Kong, Ya-Jie; Hao, Liang; Wang, Wen-Jin; Shen, Qing-Hua; Zhang, Yue-Bin; Tan, Cai-Ping.
Afiliación
  • Ling YY; MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, Sun Yat-Sen University, Guangzhou, 510006, PR China; Guangdong Basic Research Center of Excellence for Functional Molecular Engineering, Guangzhou, 510006, PR China.
  • Li ZY; MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, Sun Yat-Sen University, Guangzhou, 510006, PR China; Guangdong Basic Research Center of Excellence for Functional Molecular Engineering, Guangzhou, 510006, PR China.
  • Mu X; State Key Laboratory of Molecular Reaction, Dynamics, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, PR China.
  • Kong YJ; MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, Sun Yat-Sen University, Guangzhou, 510006, PR China; Guangdong Basic Research Center of Excellence for Functional Molecular Engineering, Guangzhou, 510006, PR China.
  • Hao L; MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, Sun Yat-Sen University, Guangzhou, 510006, PR China; Guangdong Basic Research Center of Excellence for Functional Molecular Engineering, Guangzhou, 510006, PR China.
  • Wang WJ; MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, Sun Yat-Sen University, Guangzhou, 510006, PR China; Guangdong Basic Research Center of Excellence for Functional Molecular Engineering, Guangzhou, 510006, PR China.
  • Shen QH; MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, Sun Yat-Sen University, Guangzhou, 510006, PR China; Guangdong Basic Research Center of Excellence for Functional Molecular Engineering, Guangzhou, 510006, PR China.
  • Zhang YB; State Key Laboratory of Molecular Reaction, Dynamics, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, PR China. Electronic address: zhangyb@dicp.ac.cn.
  • Tan CP; MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, Sun Yat-Sen University, Guangzhou, 510006, PR China; Guangdong Basic Research Center of Excellence for Functional Molecular Engineering, Guangzhou, 510006, PR China. Electronic address: tancaip@mail.sysu.edu.cn.
Eur J Med Chem ; 275: 116638, 2024 Sep 05.
Article en En | MEDLINE | ID: mdl-38950489
ABSTRACT
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 ß-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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Rutenio / Fármacos Fotosensibilizantes / Inmunoterapia / Proteínas de la Membrana / Antineoplásicos / Nucleotidiltransferasas Límite: Animals / Humans Idioma: En Revista: Eur J Med Chem Año: 2024 Tipo del documento: Article Pais de publicación: Francia
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Rutenio / Fármacos Fotosensibilizantes / Inmunoterapia / Proteínas de la Membrana / Antineoplásicos / Nucleotidiltransferasas Límite: Animals / Humans Idioma: En Revista: Eur J Med Chem Año: 2024 Tipo del documento: Article Pais de publicación: Francia