Nanodelivery Strategies for STING Agonists: Toward Efficient Cancer Immunotherapy

Meng Zhang,1 Yating Ji,1 Mingxia Liu,1 Yang Liu,1 Shiyu Tong,1 Yuqing Cai,1 Mengjiao Liu,2 Na Qu1 1School of Pharmaceutical Science, Liaoning University, Shenyang, 110036, People’s Republic of China; 2Institute for Experimental Molecular Imaging, RWTH Aachen University Clinic, Aachen, North Rhine-Westphalia, 52074, GermanyCorrespondence: Na Qu, Email [email protected]: cGAS-STING (cyclic GMP-AMP synthetase-interferon gene stimulator) signaling pathway has great potential in tumor treatment, and its superior performance in tumor treatment makes it a new method for tumor treatment. However, the delivery of STING agonists alone has some limitations, such as easy degradation and low bioavailability. Moreover, STING agonists are usually injected intratumorally to avoid systemic side effects caused by strong immune responses, which is not suitable for metastatic lesions. Using nanocarriers to deliver STING agonists can overcome these limitations to some extent. This review explores the collaborative foundation between nanodelivery systems and the STING signaling pathway. It systematically summarizes the existing types of STING agonists and the types of nanoscale delivery systems and analyzes the delivery strategies of STING agonist delivery systems from multiple aspects, including the tumor microenvironment (TME), tumor cell targeting, multifunctional integrated drug delivery systems, and novel biomaterial. The review elaborates on the practical applications of these strategies as well as the challenges and problems they face. Finally, it analyzes and discusses the potential future directions of STING nanodelivery systems, aiming to provide references for research in related fields and to promote the efficient application of STING agonists in cancer therapy. Keywords: cGAS-STING, Anti-tumor therapy, Drug delivery system, Synergistic basis, Delivery strategy