Advances of MnO₂ nanomaterials as novel agonists for the development of cGAS-STING-mediated therapeutics

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.