Nanomedicines harnessing cGAS-STING pathway: sparking immune revitalization to transform ‘cold’ tumors into ‘hot’ tumors

IF 27.7 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Xiaohong Ying, Qiaohui Chen, Yongqi Yang, Ziyu Wu, Wan Zeng, Chenxi Miao, Qiong Huang, Kelong Ai
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引用次数: 0

Abstract

cGAS-STING pathway stands at the forefront of innate immunity and plays a critical role in regulating adaptive immune responses, making it as a key orchestrator of anti-tumor immunity. Despite the great potential, clinical outcomes with cGAS-STING activators have been disappointing due to their unfavorable in vivo fate, signaling an urgent need for innovative solutions to bridge the gap in clinical translation. Recent advancements in nanotechnology have propelled cGAS-STING-targeting nanomedicines to the cutting-edge of cancer therapy, leveraging precise drug delivery systems and multifunctional platforms to achieve remarkable region-specific biodistribution and potent therapeutic efficacy. In this review, we provide an in-depth exploration of the molecular mechanisms that govern cGAS-STING signaling and its potential to dynamically modulate the anti-tumor immune cycle. We subsequently introduced several investigational cGAS-STING-dependent anti-tumor agents and summarized their clinical trial progress. Additionally, we provided a comprehensive review of the unique advantages of cGAS-STING-targeted nanomedicines, highlighting the transformative potential of nanotechnology in this field. Furthermore, we comprehensively reviewed and comparatively analyzed the latest breakthroughs cGAS-STING-targeting nanomedicine, focusing on strategies that induce cytosolic DNA generation via exogenous DNA delivery, chemotherapy, radiotherapy, or dynamic therapies, as well as the nanodelivery of STING agonists. Lastly, we discuss the future prospects and challenges in cGAS-STING-targeting nanomedicine development, offering new insights to bridge the gap between mechanistic research and drug development, thereby opening new pathways in cancer treatment.
利用cGAS-STING途径的纳米药物:激发免疫再生,将“冷”肿瘤转化为“热”肿瘤
cGAS-STING通路站在先天免疫的前沿,在调节适应性免疫应答中起着至关重要的作用,是抗肿瘤免疫的关键协调者。尽管潜力巨大,但由于cGAS-STING激活剂在体内的不利命运,其临床结果令人失望,这表明迫切需要创新的解决方案来弥合临床转化的差距。近年来,纳米技术的进步将cgas - sting靶向纳米药物推向了癌症治疗的前沿,利用精确的给药系统和多功能平台,实现了显著的区域特异性生物分布和强大的治疗效果。在这篇综述中,我们深入探讨了控制cGAS-STING信号的分子机制及其动态调节抗肿瘤免疫周期的潜力。我们随后介绍了几种正在研究的cgas - sting依赖性抗肿瘤药物,并总结了它们的临床试验进展。此外,我们还全面回顾了cgas - sting靶向纳米药物的独特优势,强调了纳米技术在该领域的变革潜力。此外,我们全面回顾和比较分析了以cgas -STING为靶点的纳米药物的最新突破,重点介绍了通过外源DNA递送、化疗、放疗或动态治疗诱导胞质DNA生成的策略,以及STING激动剂的纳米递送。最后,我们讨论了cgas - sting靶向纳米药物开发的未来前景和挑战,为弥合机制研究与药物开发之间的差距提供了新的见解,从而开辟了癌症治疗的新途径。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Molecular Cancer
Molecular Cancer 医学-生化与分子生物学
CiteScore
54.90
自引率
2.70%
发文量
224
审稿时长
2 months
期刊介绍: Molecular Cancer is a platform that encourages the exchange of ideas and discoveries in the field of cancer research, particularly focusing on the molecular aspects. Our goal is to facilitate discussions and provide insights into various areas of cancer and related biomedical science. We welcome articles from basic, translational, and clinical research that contribute to the advancement of understanding, prevention, diagnosis, and treatment of cancer. The scope of topics covered in Molecular Cancer is diverse and inclusive. These include, but are not limited to, cell and tumor biology, angiogenesis, utilizing animal models, understanding metastasis, exploring cancer antigens and the immune response, investigating cellular signaling and molecular biology, examining epidemiology, genetic and molecular profiling of cancer, identifying molecular targets, studying cancer stem cells, exploring DNA damage and repair mechanisms, analyzing cell cycle regulation, investigating apoptosis, exploring molecular virology, and evaluating vaccine and antibody-based cancer therapies. Molecular Cancer serves as an important platform for sharing exciting discoveries in cancer-related research. It offers an unparalleled opportunity to communicate information to both specialists and the general public. The online presence of Molecular Cancer enables immediate publication of accepted articles and facilitates the presentation of large datasets and supplementary information. This ensures that new research is efficiently and rapidly disseminated to the scientific community.
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