Inflammation-Responsive NO-Scavenging and CO-Releasing Micelles Alleviate Pulmonary Inflammation and Th2 Cytokine Production in Asthma

Abstract

Asthma is a heterogeneous and complex disorder characterized by chronic airway inflammation, presenting significant therapeutic challenges. Nitric oxide (NO) and carbon monoxide (CO) serve as pivotal gaseous signaling molecules, with elevated NO levels linked to disease exacerbation, while low-dose CO exerts anti-inflammatory effects. In this study, we engineered a dual gas-regulating micelle (DGRM) nanoplatform capable of simultaneously scavenging NO and releasing CO. In an LPS-stimulated macrophage inflammation model, DGRM demonstrated excellent biocompatibility, effectively eliminated NO and reactive oxygen species (ROS), and markedly inhibited the production of pro-inflammatory cytokines (IL-6 and IFN-γ). Furthermore, in an ovalbumin (OVA)-induced allergic asthma murine model, nebulized DGRM administration exhibited pronounced therapeutic effects. Mechanistic investigations revealed that DGRM downregulated inducible nitric oxide synthase (iNOS) while upregulating heme oxygenase-1 (HO-1), thereby modulating the iNOS/HO-1/CO signaling axis. These findings collectively indicate that DGRM effectively mitigates airway inflammation in allergic asthma, offering a gasotransmitter-based nanotherapeutic approach for asthma management.