Engineered responsive-hydrogels drive cGAS-STING pathway activation for cancer immunotherapy

The cGAS-STING pathway holds considerable promise for cancer immunotherapy, yet its clinical translation is generally constrained by a narrow therapeutic window and the risk of systemic inflammation, making precision activation a central challenge. Engineered hydrogels provide a compelling strategy by serving as injectable, tissue-adherent depots that enable prolonged retention and programmable release within the tumor microenvironment. This review first outlines the immunological rationale and therapeutic window for cGAS-STING activation, then surveys hydrogel engineering strategies, including cargo loading, affinity-based retention, and stimuli-responsive release to effectively couple release kinetics with spatiotemporal immune activation profiles. We further examine hydrogel-enabled combinational regimens, emphasizing temporal programming and staged activation. While hydrogel platforms are well-positioned to bridge the gap between spatiotemporally controlled release and immune microenvironment remodeling, additional technological refinement, manufacturing-ready "minimalist intelligence" and accelerated translational and regulatory alignment are essential to realize their full clinical potential.