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Multifunctional single-component photosensitizers as metal-free ferroptosis inducers for enhanced photodynamic immunotherapy.
Fang, Laiping; Meng, Qi; Wang, Jizhuang; Tu, Yike; Qu, Hong; Diao, Yanzhao; Li, Wuming; Wen, Hua; Fang, Jin; Hang, Lifeng; Ma, Ping'an; Jiang, Guihua.
Afiliación
  • Fang L; Guangdong Second Provincial General Hospital, Postdoctoral Research Station of Basic Medicine, School of Medicine, Jinan University, Xingangzhong Road 466, Guangzhou 518037, PR China.
  • Meng Q; State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Renmin Street 5625, Changchun 130012, PR China.
  • Wang J; College of Chemistry and Materials Science, Jinan University, Huangpu Avenue West 601, Guangzhou 510632, PR China.
  • Tu Y; Guangzhou Key Laboratory of Molecular Functional Imaging and Artificial Intelligence for Major Brain Diseases, The Department of Medical Imaging, Guangdong Second Provincial General Hospital, Xingangzhong Road 466, Guangzhou 518037, PR China.
  • Qu H; Guangzhou Key Laboratory of Molecular Functional Imaging and Artificial Intelligence for Major Brain Diseases, The Department of Medical Imaging, Guangdong Second Provincial General Hospital, Xingangzhong Road 466, Guangzhou 518037, PR China.
  • Diao Y; Guangzhou Key Laboratory of Molecular Functional Imaging and Artificial Intelligence for Major Brain Diseases, The Department of Medical Imaging, Guangdong Second Provincial General Hospital, Xingangzhong Road 466, Guangzhou 518037, PR China.
  • Li W; Guangzhou Key Laboratory of Molecular Functional Imaging and Artificial Intelligence for Major Brain Diseases, The Department of Medical Imaging, Guangdong Second Provincial General Hospital, Xingangzhong Road 466, Guangzhou 518037, PR China.
  • Wen H; Guangzhou Key Laboratory of Molecular Functional Imaging and Artificial Intelligence for Major Brain Diseases, The Department of Medical Imaging, Guangdong Second Provincial General Hospital, Xingangzhong Road 466, Guangzhou 518037, PR China.
  • Fang J; Guangzhou Key Laboratory of Molecular Functional Imaging and Artificial Intelligence for Major Brain Diseases, The Department of Medical Imaging, Guangdong Second Provincial General Hospital, Xingangzhong Road 466, Guangzhou 518037, PR China.
  • Hang L; Guangzhou Key Laboratory of Molecular Functional Imaging and Artificial Intelligence for Major Brain Diseases, The Department of Medical Imaging, Guangdong Second Provincial General Hospital, Xingangzhong Road 466, Guangzhou 518037, PR China. Electronic address: hanglf@ustc.edu.cn.
  • Ma P; State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Renmin Street 5625, Changchun 130012, PR China. Electronic address: mapa675@ciac.ac.cn.
  • Jiang G; Guangzhou Key Laboratory of Molecular Functional Imaging and Artificial Intelligence for Major Brain Diseases, The Department of Medical Imaging, Guangdong Second Provincial General Hospital, Xingangzhong Road 466, Guangzhou 518037, PR China. Electronic address: jianggh@gd2h.org.cn.
Acta Biomater ; 186: 383-395, 2024 Sep 15.
Article en En | MEDLINE | ID: mdl-39069112
ABSTRACT
Immunotherapy can enhance primary tumor efficacy, restrict distant growth, and combat lung metastasis. Unfortunately, it remains challenging to effectively activate the immune response. Here, tertiary butyl, methoxy, and triphenylamine (TPA) were utilized as electron donors to develop multifunctional photosensitizers (PSs). CNTPA-TPA, featuring TPA as the donor (D) and cyano as the acceptor (A), excelled in reactive oxygen species (ROS) generation due to its smaller singlet-triplet energy gap (ΔES-T) and larger spin-orbit coupling constant (SOC). Additionally, cyano groups reacted with glutamate (Glu) and glutathione (GSH), reducing intracellular GSH levels. This not only enhanced PDT efficacy but also triggered redox dyshomeostasis-mediated ferroptosis. The positive effects of photodynamic therapy (PDT) and ferroptosis promoted immunogenic cell death (ICD) and immune activation. By further combining anti-programmed cell death protein ligand-1 (anti-PD-L1) antibody, the powerful treatments of ferroptosis-assisted photodynamic immunotherapy significantly eradicated the primary tumors, inhibited the growth of distant tumors, and suppressed lung metastasis. In this study, a three-pronged approach was realized by single-component CNTPA-TPA, which simultaneously served as metal-free ferroptosis inducers, type-I photosensitizers, and immunologic adjuvants for near-infrared fluorescence imaging (NIR FLI)-guided multimodal phototheranostics of tumor. STATEMENT OF

SIGNIFICANCE:

(1) CNTPA-TPA shared the smallest singlet-triplet energy gap and the largest spin-orbit coupling constant, which boosted intersystem crossing for efficient type-I photodynamic therapy (PDT); (2) Special reactions between cyano groups with glutamate and glutathione in mild conditions restricted the biosynthesis of intracellular GSH. GSH-depletion efficiently induced glutathione peroxidase 4 inactivation and lipid peroxide, resulting in ferroptosis of tumor cells; (3) The combination treatments of ferroptosis-assisted photodynamic immunotherapy induced by single-component CNTPA-TPA with the participation of anti-PD-L1 antibody resulted in increased T-cell infiltration and profound suppression of both primary and distant tumor growth, as well as lung metastasis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fotoquimioterapia / Fármacos Fotosensibilizantes / Ferroptosis / Inmunoterapia Límite: Animals / Female / Humans Idioma: En Revista: Acta Biomater Año: 2024 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fotoquimioterapia / Fármacos Fotosensibilizantes / Ferroptosis / Inmunoterapia Límite: Animals / Female / Humans Idioma: En Revista: Acta Biomater Año: 2024 Tipo del documento: Article Pais de publicación: Reino Unido