作为一种必需的微量营养素,锰在生理过程和免疫过程中起着重要作用。近几十年来,cGAS-STING途径,它可以先天性识别外源和内源DNA进行激活,已被广泛报道在一些重要疾病的先天免疫中起关键作用,如感染和肿瘤。锰离子(Mn2+)最近已被证明与cGAS特异性结合并激活cGAS-STING途径作为潜在的cGAS激动剂,然而,Mn2+的低稳定性显著限制了其进一步的医学应用。作为锰最稳定的形式之一,据报道,二氧化锰(MnO2)纳米材料显示出多种有前途的功能,如药物输送,抗肿瘤和抗感染活性。更重要的是,MnO2纳米材料也被发现通过转化为Mn2+作为cGAS激动剂的潜在候选物,这表明它们在不同疾病条件下的cGAS-STING法规的潜力。在这次审查中,介绍了MnO2纳米材料的制备方法及其生物活性。此外,我们着重介绍了cGAS-STING途径,并讨论了MnO2纳米材料转化为Mn2活化cGAS的详细机理。并讨论了MnO2纳米材料通过调控cGAS-STING通路在疾病治疗中的应用,这可能有利于基于MnO2纳米平台的新型cGAS-STING靶向治疗的未来发展。
As an essential micronutrient, manganese plays an important role in the physiological process and immune process. In recent decades, cGAS-STING pathway, which can congenitally recognize exogenous and endogenous DNA for activation, has been widely reported to play critical roles in the innate immunity against some important diseases, such as infections and tumor. Manganese ion (Mn2+) has been recently proved to specifically bind with cGAS and activate cGAS-STING pathway as a potential cGAS agonist, however, is significantly restricted by the low stability of Mn2+ for further medical application. As one of the most stable forms of manganese, manganese dioxide (MnO2) nanomaterials have been reported to show multiple promising functions, such as drug delivery, anti-tumor and anti-infection activities. More importantly, MnO2 nanomaterials are also found to be a potential candidate as cGAS agonist by transforming into Mn2+, which indicates their potential for cGAS-STING regulations in different diseased conditions. In this review, we introduced the methods for the preparation of MnO2 nanomaterials as well as their biological activities. Moreover, we emphatically introduced the cGAS-STING pathway and discussed the detailed mechanisms of MnO2 nanomaterials for cGAS activation by converting into Mn2+. And we also discussed the application of MnO2 nanomaterials for disease treatment by regulating cGAS-STING pathway, which might benefit the future development of novel cGAS-STING targeted treatments based on MnO2 nanoplatforms.