Figure 2.

Mechanism for the conversion of MnO₂ nanomaterials into Mn²⁺ to activate cGAS-STING pathway. MnO₂ nanomaterials can undergo redox reactions with GSH and H₂O₂ in acidic tumor environments to consume excessive GSH and H₂O₂ in tumor environments. In response, Mn²⁺ is released, and the generated O₂ can improve the tumor hypoxia state. Mn²⁺ enhances the ability of cGAS to recognize dsDNA from bacteria, tumor cells, viruses and mitochondria in the environment, and promotes the production of 2’,3’ - cyclic GMP AMP (2’,3’ - cGAMP). cGAMP binds to interferon gene stimulator (STING), resulting in tank binding kinase 1 (TBK1) dependent phosphorylation (P) of interferon regulator 3 (IRF3). The active IRF3 dimer transfers to the nucleus and activates the transcription of type I interferon gene. STING can also activate IκB kinase (IKK), phosphorylated NF-κB Inhibitory Protein IκB α, Lead to polyubiquitination and degradation, and then NF-κB can enter the nucleus and start the transcription of immune stimulating genes.