Disruption of Zinc Homeostasis by a Novel Platinum(IV)‐Terthiophene Complex for Antitumor Immunity

Autor: Xuxian Su, Bin Liu, Wen‐Jin Wang, Kun Peng, Bing‐Bing Liang, Yue Zheng, Qian Cao, Zong‐Wan Mao
Rok vydání: 2023
Předmět:
Zdroj: Angewandte Chemie. 135
ISSN: 1521-3757
0044-8249
Popis: Zinc homeostatic medicine is of great potential for cancer chemo-immunotherapy, however, there are few reports on anti-tumor compounds that can trigger Zn2+-mediated immune responses. In this work, we developed a novel cyclometalated Pt(IV)-terthiophene complex Pt3, not only inducing DNA damage and cellular metabolism dysregulation, but also disrupting zinc homeostasis as indicated by the abnormal transcriptional level of zinc regulatory proteins, excess accumulation of Zn2+ in cytoplasm, and down-regulation of metallothioneins (MTs), which further caused redox imbalance. The simultaneous disruption of zinc and redox homeostasis in response to Pt3 treatment activated gasdermin-D mediated pyroptosis accompanied with cytoskeleton remodeling, thus releasing pro-inflammatory cytokines to promote dendritic cells (DCs) maturation and T cells tumor-infiltration, eventually eliminating both primary and distant tumors in vivo. As far as we know, this is the first metal complex that can regulate zinc homeostasis to activate anti-tumor immunity.
Databáze: OpenAIRE
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