1. A Carbonic Anhydrase IX (CAIX)-Anchored Rhenium(I) Photosensitizer Evokes Pyroptosis for Enhanced Anti-Tumor Immunity.
- Author
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Su X, Wang WJ, Cao Q, Zhang H, Liu B, Ling Y, Zhou X, and Mao ZW
- Subjects
- Animals, Antigens, Neoplasm metabolism, Antineoplastic Agents chemical synthesis, Antineoplastic Agents chemistry, Breast Neoplasms metabolism, Breast Neoplasms pathology, Carbonic Anhydrase IX metabolism, Carbonic Anhydrase Inhibitors chemical synthesis, Carbonic Anhydrase Inhibitors chemistry, Cell Death drug effects, Cell Line, Cell Proliferation drug effects, Coordination Complexes chemical synthesis, Coordination Complexes chemistry, Dendritic Cells drug effects, Dose-Response Relationship, Drug, Drug Screening Assays, Antitumor, Female, Humans, Mammary Neoplasms, Experimental drug therapy, Mammary Neoplasms, Experimental metabolism, Mammary Neoplasms, Experimental pathology, Mice, Mice, Inbred BALB C, Photochemotherapy, Photosensitizing Agents chemical synthesis, Photosensitizing Agents chemistry, Pyroptosis drug effects, Rhenium chemistry, Rhenium pharmacology, Structure-Activity Relationship, T-Lymphocytes drug effects, Tumor Hypoxia drug effects, Tumor Microenvironment drug effects, Antineoplastic Agents pharmacology, Breast Neoplasms drug therapy, Carbonic Anhydrase IX antagonists & inhibitors, Carbonic Anhydrase Inhibitors pharmacology, Coordination Complexes pharmacology, Photosensitizing Agents pharmacology
- Abstract
An ideal cancer treatment should not only destroy primary tumors but also improve the immunogenicity of the tumor microenvironment to achieve a satisfactory anti-tumor immune effect. We designed a carbonic anhydrase IX (CAIX)-anchored rhenium(I) photosensitizer, named CA-Re, that not only performs type-I and type-II photodynamic therapy (PDT) with high efficiency under hypoxia (nanomolar-level phototoxicity), but also evokes gasdermin D (GSDMD) mediated pyroptotic cell death to effectively stimulate tumor immunogenicity. CA-Re could disrupt and self-report the loss of membrane integrity simultaneously. This promoted the maturation and antigen-presenting ability of dendritic cells (DCs), and fully activated T cells dependent adaptive immune response in vivo, eventually eliminating distant tumors at the same time as destroying primary tumors. To the best of our knowledge, CA-Re is the first metal complex-based pyroptosis inducer., (© 2021 Wiley-VCH GmbH.)
- Published
- 2022
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