Mitochondrion-Targeted Type I Photodynamic Therapy for Agonist Independent cGAS-STING Activation

Mitochondrion-Targeted Type I Photodynamic Therapy for Agonist Independent cGAS-STING Activation

© 2025 Wiley‐VCH GmbH.

Détails bibliographiques
Publié dans:Advanced materials (Deerfield Beach, Fla.). - 1998. - 37(2025), 14 vom: 09. Apr., Seite e2418894
Auteur principal: Xu, Yin (Auteur)
Autres auteurs: An, Daokuan, Zhang, Tian, Wu, Xiaochen, Wang, Shuang, Shao, Jinjun, Qu, Lu-Lu, Guo, Yuxin, Dong, Xiaochen
Format: Article en ligne
Langue:English
Publié: 2025
Accès à la collection:Advanced materials (Deerfield Beach, Fla.)
Sujets:Journal Article cGAS‐STING activation cancer immunotherapy mitochondrion targeting nanozyme photodynamic therapy Photosensitizing Agents Membrane Proteins Gold 7440-57-5 plus... Nucleotidyltransferases EC 2.7.7.- Silicon Dioxide 7631-86-9 STING1 protein, human cGAS protein, human Boron Compounds
Description
Résumé:© 2025 Wiley‐VCH GmbH.
CGAS-STING agonists generally lead to hyperimmunity and systemic toxicity, hindering their immunotherapeutic outcomes. Herein, a mitochondrion-targeted nanoagonist (termed HABH) containing boron dipyrromethene (BODIPY)-derived type I photosensitizer (BDP) and Au nanoparticle-engineered hollow mesoporous silica (HMSN/AuNPs) has been fabricated for light-controlled mitochondrial stress-inducing and agonist-independent cGAS-STING pathway activation. The HABH nanoagonist can actively target tumor tissues and release the mitochondrion-targeted BDP. Under light illumination, BDP achieves type I photodynamic therapy (PDT) in mitochondria, generating massive hydroxyl radicals (•OH) and inducing mitochondrial stress in an oxygen-independent manner, promoting the release of mitochondrial DNA (mtDNA). Simultaneously, the HMSN/AuNPs act as dual nanozymes to derive cascade reactions for •OH production, elevating the intracellular oxidative state, and together with the BDP-induced mitochondrial stress, finally evoking the cGAS-STING pathway and facilitating the release of type I interferon. In the orthotopic breast tumor models, the HABH nanoagonist achieved intratumoral and systemic immunoactivation for eradicating primary tumors and preventing metastasis tumors. Therefore, the constructed mitochondrion-targeted nanoagonist enabled light-controlled and agonist-independent cGAS-STING activation, providing a paradigm for photoimmunotherapy
Description:Date Completed 10.04.2025
Date Revised 10.04.2025
published: Print-Electronic
Citation Status MEDLINE
ISSN:1521-4095
DOI:10.1002/adma.202418894