Enhancing nano-immunotherapy of cancer through cGAS–STING pathway modulation

Activation of the cyclic guanosine monophosphate–adenosine monophosphate synthase (cGAS)–stimulator of interferon genes (STING) pathway plays a critical role in cancer immunotherapy due to the secretion of multiple pro-inflammatory cytokines and chemokines. Numerous cGAS–STING agonists have been developed for preclinical and clinical trials in tumor immunity. However, several obstacles, such as agonist molecules requiring multiple doses, rapid degradation and poor targeting, weaken STING activation at the tumor site. The advancement of nanotechnology provides an optimized platform for the clinical application of STING agonists. In this review, we summarize events of cGAS–STING pathway activation, the dilemma of delivering STING agonists, and recent advances in the nano-delivery of cGAS–STING agonist formulations for enhancing tumor immunity. Furthermore, we address the future challenges associated with STING-based therapies and offer insights to guide subsequent clinical applications.