Platinum‐Based Strategies for cGAS‐STING Activation: From Molecular Design to Nanomedicine

ABSTRACT

Platinum‐based drugs remain the cornerstone of chemotherapy for various solid tumors. However, their clinical efficacy is limited by systemic toxicities, acquired resistance, and the inability to induce sufficient, durable antitumor immunity. In this context, targeting the cyclic GMP‐AMP synthase (cGAS)‐stimulator of interferon genes (STING) pathway has become a key strategy in modern cancer immunotherapy. Notably, platinum complexes inherently possess the ability to activate this innate immune signaling pathway, primarily through the induction of cytosolic double‐stranded DNA (dsDNA) accumulation. This activation promotes tumor cell apoptosis and enhances antitumor immunity by facilitating antigen presentation, promoting dendritic cell (DC) maturation, and boosting T cell activation. Herein, we review recent advances in platinum‐based STING activators for chemoimmunotherapy. First, mechanisms linking classical platinum cytotoxicity to cGAS‐STING signaling activation are summarized. Subsequently, emerging strategies are systematically categorized into molecular design and nanomedicine approaches. Molecular designs are grouped by the functional ligands attached to platinum scaffolds, while advanced nanoplatforms are arranged according to carrier materials and architectures. Finally, we highlight the remaining challenges in this field and outline potential directions for the development of next‐generation chemoimmunotherapy.