Lu Yanjun, Li Zhiyan, Zhu Xudong, Zeng Qingwei, Liu Song, Guan Wenxian
Division of Gastric Surgery, Department of General Surgery, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, People's Republic of China.
Division of Thoracic Surgery, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, People's Republic of China.
Int J Nanomedicine. 2025 Jan 6;20:181-197. doi: 10.2147/IJN.S503780. eCollection 2025.
The microenvironment tends to be immunosuppressive during tumor growth and proliferation. Immunotherapy has attracted much attention because of its ability to activate tumor-specific immune responses for tumor killing. The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway is an innate immune pathway that activates antitumor immunity by producing type I interferons. Cyclic dinucleotides (CDNs), produced by cGAS sensing cytoplasmic abnormal DNA, are major intermediate activating molecules in the STING pathway. Nowadays, CDNs and their derivatives have widely worked as powerful STING agonists in tumor immunotherapy. However, their clinical translation is hindered by the negative electrical properties, sensitivity to hydrolytic enzymes, and systemic toxicity. Recently, various CDN delivery systems have made significant progress in addressing these issues, either through monotherapy or in combination with other treatment modalities. This review details recent advances in CDNs-based pharmaceutical development or delivery strategies for enriching CDNs at tumor sites and activating the STING pathway.
在肿瘤生长和增殖过程中，微环境往往具有免疫抑制作用。免疫疗法因其能够激活肿瘤特异性免疫反应以杀伤肿瘤而备受关注。环磷酸鸟苷-腺苷合成酶-干扰素基因刺激因子（cGAS-STING）通路是一条天然免疫通路，通过产生I型干扰素激活抗肿瘤免疫。由cGAS感知细胞质异常DNA产生的环二核苷酸（CDNs）是STING通路中的主要中间激活分子。如今，CDNs及其衍生物在肿瘤免疫治疗中已广泛作为强大的STING激动剂发挥作用。然而，它们的临床转化受到负电性质、对水解酶的敏感性和全身毒性的阻碍。最近，各种CDN递送系统在解决这些问题方面取得了重大进展，无论是通过单一疗法还是与其他治疗方式联合使用。本文综述了基于CDNs的药物开发或递送策略的最新进展，这些策略可在肿瘤部位富集CDNs并激活STING通路。
