Medical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, 450001, China.
The Center of Infection and Immunity, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, Henan, 450001, China.
Adv Healthc Mater. 2023 Jul;12(19):e2300260. doi: 10.1002/adhm.202300260. Epub 2023 Mar 20.
As the first line of host defense against pathogenic infections, innate immunity plays a key role in antitumor immunotherapy. The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) (cGAS-STING) pathway has attracted much attention because of the secretion of various proinflammatory cytokines and chemokines. Many STING agonists have been identified and applied into preclinical or clinical trials for cancer immunotherapy. However, the fast excretion, low bioavailability, nonspecificity, and adverse effects of the small molecule STING agonists limit their therapeutic efficacy and in vivo application. Nanodelivery systems with appropriate size, charge, and surface modification are capable of addressing these dilemmas. In this review, the mechanism of the cGAS-STING pathway is discussed and the STING agonists, focusing on nanoparticle-mediated STING therapy and combined therapy for cancers, are summarized. Finally, the future direction and challenges of nano-STING therapy are expounded, emphasizing the pivotal scientific problems and technical bottlenecks and hoping to provide general guidance for its clinical application.
作为宿主防御致病感染的第一道防线，先天免疫在抗肿瘤免疫治疗中发挥着关键作用。环鸟苷酸-腺苷酸合酶（cGAS）-干扰素基因刺激物（STING）（cGAS-STING）途径由于分泌各种促炎细胞因子和趋化因子而受到广泛关注。已经鉴定出许多 STING 激动剂，并将其应用于癌症免疫治疗的临床前或临床试验中。然而，小分子 STING 激动剂的快速排泄、低生物利用度、非特异性和不良反应限制了它们的治疗效果和体内应用。具有适当大小、电荷和表面修饰的纳米递药系统能够解决这些难题。本文讨论了 cGAS-STING 途径的机制，并总结了 STING 激动剂，重点介绍了基于纳米颗粒的 STING 治疗和癌症的联合治疗。最后，阐述了纳米 STING 治疗的未来方向和挑战，强调了关键的科学问题和技术瓶颈，希望为其临床应用提供一般性指导。
