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

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 Mn²⁺, Zn²⁺ and Ca²⁺, 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.