Metal-based nanoparticles promote the activation of cGAS-STING pathway for enhanced cancer immunotherapy
Yue Li, Zirui Zhu, Shiyuan Hua, Yinghong Wan, Qin Chen, Ge Gao, Hong Zhang, Wei Duan, Wei Zheng, Yong Guo, Quan Hu, Jia‐Wei Shen, Min Zhou, Qiaolin Wei
Abstract
Immunotherapy occupies an increasingly important place in the field of tumor treatment. The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway, which is responsible for sensing and responding to cytosolic DNA, stands out as a key player of the host innate immunity and a significant contributor to anti-tumor immunotherapy. Besides, it serves as the principal signaling pathway for type I interferon (IFN) production, coordinating the maturation and activation of various immune cells like dendritic cells (DCs) and CD8 + T cells, thus bridging innate and adaptive immunity. The increasing focus on essential metal nanoparticles, notably Mn 2+ , Zn 2+ and Ca 2+ , and their roles in the induction of oxidative stress are of increasing interest in the application of tumor immunotherapy especially for the stimulation of cGAS-STING pathway. Recent advancements in metal-based nanomaterials present a promising avenue for anti-tumor immunotherapy based on cGAS-STING pathway activation. This review offers a comprehensive overview of how metal-based nanomaterials affect the cGAS-STING pathway, as well as discusses the latest findings on metal-based nanomaterials, providing insights into their potential uses in cancer immunotherapy grounded in the activation of the cGAS-STING pathway. • Metal-based nanoparticles could enhance or directly activate the cGAS-STING pathway in tumor therapy. • The activation mechanism of metal-based nanoparticles in cGAS-STING pathway were summarized. • The most recent and representative examples of metal ions-based cGAS-STING nano agonists for cancer treatment were presented. • The prospects and potential challenges of metal-based nanoparticles-activated metalloimmunotherapy based on the cGAS-STING pathway.