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纳米颗粒介导的 STING 激动剂递呈用于增强癌症免疫治疗。

Nanoparticle-Mediated STING Agonist Delivery for Enhanced Cancer Immunotherapy.

机构信息

CAS Key Laboratory of Soft Matter Chemistry, Department of Polymer Science and Engineering, University of Science and Technology of China, Hefei, Anhui, 230026, China.

出版信息

Macromol Biosci. 2021 Aug;21(8):e2100133. doi: 10.1002/mabi.202100133. Epub 2021 Jun 12.

Abstract

Stimulator of interferon genes (STING) are located in the endoplasmic reticulum of cells, which have been demonstrated to show considerable potentials to achieve efficient antitumor immunity by inducing various pro-inflammatory cytokines and chemokines, such as type I interferons. A variety of STING agonists have been prepared for STING activation, and many of them have been promoted to preclinical trials or clinical applications for the immunotherapy of cancers. However, the intrinsic disadvantages of the small molecule STING agonists can limit the in vivo application and final therapeutic efficacy due to low bioavailability of targeting tissues. Moreover, a cascade of physiological barriers for in vivo STING activation also limit the accumulation of STING agonists in targeting tissues. Drug delivery systems play an important role to improve the STING activation efficiency. In recent years, a variety of nanoparticle-mediated STING agonist delivery systems have been engineered and exploited to address the challenges related to the in vivo STING activation, including liposomes, polymeric micelles, polymersomes, and so on. In this review article, the progresses concerning STING agonists and related delivery systems in recent years will be summarized and discussed.

摘要

干扰素基因刺激物 (STING) 位于细胞的内质网中,已被证明通过诱导各种促炎细胞因子和趋化因子(如 I 型干扰素)具有实现有效抗肿瘤免疫的巨大潜力。已经制备了多种 STING 激动剂以激活 STING,其中许多已经被推进到临床前试验或临床应用中用于癌症的免疫治疗。然而,小分子 STING 激动剂的内在缺点可能会由于靶向组织的生物利用度低而限制其体内应用和最终治疗效果。此外,体内 STING 激活的一系列生理屏障也限制了 STING 激动剂在靶向组织中的积累。药物递送系统在提高 STING 激活效率方面发挥着重要作用。近年来,已经设计和利用了多种基于纳米颗粒的 STING 激动剂递送系统来解决与体内 STING 激活相关的挑战,包括脂质体、聚合物胶束、聚合物囊泡等。在这篇综述文章中,将总结和讨论近年来有关 STING 激动剂和相关递送系统的进展。

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