Activation of cGAS-STING axis by CO@OMVs promote macrophage mitophagy for CIRI treatment.

Abstract

This study investigates the effects of nanobody-engineered bacterial outer membrane vesicles (CO@OMVs) on cGAS-STING-associated signaling, macrophage mitophagy, and cerebral ischemia-reperfusion injury (CIRI). Following extraction and characterization of CO@OMVs, in vitro experiments in RAW 264.7 macrophages demonstrated increased levels of cGAS-STING-associated signaling molecules, enhanced mitophagy, increased tumor necrosis factor-α (TNF-α) secretion, and decreased IL-6 secretion. In a CIRI mouse model, CO@OMVs reduced local inflammatory markers and apoptosis and improved cognitive and neurobehavioral functions. Multi-omics analyses further supported the therapeutic potential of CO@OMVs in mitigating early brain injury.