Zhu Shuxuan, Xu Wenfei, Li Hongxia, Sun Zhaogang, Zhu Ying, Liu Wenjing, Chu Hongqian
Translational Medicine Center, Beijing Chest Hospital, Beijing Tuberculosis and Thoracic Tumor Research Institute, Capital Medical University, Beijing, 101149, China.
Department of Medical Oncology, Beijing Chest Hospital, Beijing Tuberculosis and Thoracic Tumor Research Institute, Capital Medical University, Beijing, 101149, China.
J Nanobiotechnology. 2025 Aug 21;23(1):578. doi: 10.1186/s12951-025-03669-4.
Despite the major breakthroughs in immunotherapy, a substantial number of cancer patients continue to confront problems such as low response rates, which restrict the overall effectiveness of existing treatments. There is an urgent necessity to combine advanced biomedical advancements with conventional therapies to improve treatment results. The activation of the cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING) pathway has become a viable technique to elicit innate immune responses against tumors, attracting significant interest as a novel target in cancer therapy. However, STING agonists face significant challenges in clinical application due to complications related to transport efficiency, degradation, and bioavailability. Recent breakthroughs in nanotechnology have facilitated the invention of metal-organic frameworks (MOFs) as adaptable platforms for cancer immunotherapy, utilizing their distinctive characteristics, including large surface area, adjustable porosity, and improved permeability. This review systematically investigates current advancements in the usage of MOFs for altering the cGAS-STING pathway, highlighting their promise as adaptable platforms for agonist administration or direct activation in tumor immunotherapy. Additionally, this review focuses on the use of MOFs as carriers or agonists, integrated with multimodal strategies to potentiate anticancer immune responses via the cGAS-STING pathway. The discussion concludes with an examination of the challenges and future directions for MOFs in boosting immunotherapy through the stimulation of the cGAS-STING pathway.
尽管免疫疗法取得了重大突破，但仍有相当数量的癌症患者继续面临诸如低反应率等问题，这限制了现有治疗方法的整体疗效。迫切需要将先进的生物医学进展与传统疗法相结合，以提高治疗效果。环磷酸鸟苷-腺苷酸合成酶（cGAS）和干扰素基因刺激因子（STING）通路的激活已成为引发针对肿瘤的先天免疫反应的一种可行技术，作为癌症治疗的新靶点引起了广泛关注。然而，由于与转运效率、降解和生物利用度相关的并发症，STING激动剂在临床应用中面临重大挑战。纳米技术的最新突破促进了金属有机框架（MOF）作为癌症免疫治疗适应性平台的发明，利用了它们的独特特性，包括大表面积、可调节孔隙率和改善的渗透性。本文系统地研究了MOF在改变cGAS-STING通路方面的当前进展，强调了它们作为肿瘤免疫治疗中激动剂给药或直接激活的适应性平台的潜力。此外，本文重点关注MOF作为载体或激动剂的应用，与多模式策略相结合，通过cGAS-STING通路增强抗癌免疫反应。讨论最后审视了MOF在通过刺激cGAS-STING通路促进免疫治疗方面面临的挑战和未来方向。
