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Simultaneous Photoactivation of cGAS-STING Pathway and Pyroptosis by Platinum(II) Triphenylamine Complexes for Cancer Immunotherapy.

Yu-Yi LingXiao-Yu XiaLiang HaoWen-Jin WangHang ZhangLiu-Yi LiuWenting LiuZhi-Yuan LiCai-Ping TanZong-Wan Mao
Published in: Angewandte Chemie (International ed. in English) (2022)
Activation of the cyclic GMP-AMP synthase-stimulator of the interferon gene (cGAS-STING) pathway is a potent anticancer immunotherapeutic strategy, and the induction of pyroptosis is a feasible way to stimulate the anticancer immune responses. Herein, two Pt<sup>II</sup> complexes (Pt1 and Pt2) were designed as photoactivators of the cGAS-STING pathway. In response to light irradiation, Pt1 and Pt2 could damage mitochondrial/nuclear DNA and the nuclear envelope to activate the cGAS-STING pathway, and concurrently induce pyroptosis in cancer cells, which evoked an intense anticancer immune response in vitro and in vivo. Overall, we present the first photoactivator of the cGAS-STING pathway, which may provide an innovative design strategy for anticancer immunotherapy.
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