Metal-based nanoparticles promote the activation of cGAS-STING pathway for enhanced cancer immunotherapy

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.