MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, State Key Laboratory of Oncology in South China, Sun Yat-Sen University, Guangzhou, 510006, P. R. China.
Angew Chem Int Ed Engl. 2022 Oct 24;61(43):e202210988. doi: 10.1002/anie.202210988. Epub 2022 Sep 23.
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 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.
环鸟苷酸-腺苷酸合酶-干扰素基因刺激物（cGAS-STING）途径的激活是一种有效的癌症免疫治疗策略，而细胞焦亡的诱导是刺激抗癌免疫反应的一种可行方法。在此，设计了两种铂配合物（Pt1 和 Pt2）作为 cGAS-STING 途径的光激活剂。在光照射下，Pt1 和 Pt2 可以破坏线粒体/核 DNA 和核膜，激活 cGAS-STING 途径，并同时诱导癌细胞发生细胞焦亡，从而在体外和体内引发强烈的抗癌免疫反应。总之，我们提出了第一个 cGAS-STING 途径的光激活剂，这可能为癌症免疫治疗提供了一种创新的设计策略。
