Nano-delivery of STING agonists: Unraveling the potential of immunotherapy

The cyclic GMP-AMP synthetase-interferon gene stimulator (cGAS-STING) pathway possesses tremendous potential in immune responses, viral defense, and anti-tumor treatment. Currently, an increasing number of nanocarriers are being engineered to convey STING agonists, with the goal of booSTING the conveying capacity of cGAS-STING agonists and augment the therapeutic potency of STING agonists. In this review, we explore the mechanisms of cGAS-STING activators, the application of different nanocarriers in the STING pathway, and the application of nanocarriers in anti-tumor therapy, antiviral therapy and autoimmune diseases. Additionally, we also discuss the adverse effects of STING pathway activation and the challenges encountered in nano delivery, we hope that future research will delve into the development of new nanocarriers and the clinical translation of nanocarriers in STING-mediated immunotherapy. STATEMENT OF SIGNIFICANCE: The cyclic GMP-AMP synthetase-interferon gene stimulator (cGAS-STING) pathway possesses tremendous potential in immune responses, viral defense, and anti-tumor treatment. In this review, we first explore the activation mechanism of cGAS-STING signal pathway and the diverse array of nanocarriers that have been employed in the context of the STING pathway, such as natural carrier, lipid nanoparticles, polymeric nanoparticles, and inorganic nanoparticles, highlighting their unique properties and the challenges they present in clinical applications. Furthermore, we discuss the research progress regarding nanocarriers in STING-mediated immunotherapy, such as the application of nanocarriers in anti-tumor therapy, antiviral therapy and autoimmune diseases therapy. Finally, the side effects of STING pathway activation and the issues encountered in nano delivery will be discussed, hoping that future research will delve into the development of new nanocarriers and the clinical translation of nanocarriers in STING-mediated immunotherapy.