Novel emerging nano-assisted anti-cancer strategies based on the STING pathway

Xianghui Li, Haoran Wang, Yuanyuan Chen, Zhiyan Li, Song Liu, Wenxian Guan, Youkun Lin, Cunwei Cao, Wenjun Zheng, Jinhui Wu
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Abstract

Activation of simulator of interferon genes (STING), which induces the production of proinflammatory factors and immune effector cell activation, is considered a promising strategy for enhanced anti-cancer intervention. However, several obstacles prevent STING signaling in solid tumors, such as delivered molecules’ rapid degradation, restriction to tumor sites, insufficient intracellular concentrations, and low responsivity. Well-designed, multifunctional nano-formulations have emerged as optimized platforms for STING activation. Recently, a variety of nano-formulations have been developed and used in STING activation, thus facilitating immunotherapy in preclinical and clinical stages. Herein, we summarize recent advances in nanotechnology-based delivery, activation, and application strategies, which have advanced various aspects of immunotherapy. Novel STING agonists and their mechanisms in STING-activation-mediated tumor interventions are highlighted herein, to provide a comprehensive overview and discuss future directions for boosting immunotherapy via STING regulation.
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基于STING通路的新型纳米辅助抗癌策略
干扰素基因模拟器(STING)的激活可诱导促炎因子的产生和免疫效应细胞的激活,被认为是增强抗癌干预的一种有前途的策略。然而,实体肿瘤中存在一些阻碍STING信号传导的障碍,如递送分子的快速降解、对肿瘤部位的限制、细胞内浓度不足和低响应性。精心设计的多功能纳米配方已经成为STING活化的优化平台。近年来,各种纳米制剂已被开发并用于STING激活,从而促进了临床前和临床阶段的免疫治疗。在此,我们总结了基于纳米技术的递送、激活和应用策略的最新进展,这些进展促进了免疫治疗的各个方面。本文重点介绍了新型STING激动剂及其在STING激活介导的肿瘤干预中的作用机制,全面概述了通过STING调节促进免疫治疗的未来方向。
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