Single H2S molecule mediates three-stage antibacterial and immunomodulatory effects in dendritic mesoporous organosilica (DMOS-4MPBA) nanoplatform.

Bacterial infections and inflammatory diseases pose a severe global health threat, driven by antibiotic resistance and dysregulated immune responses. To overcome these challenges, we designed redox-responsive dendritic mesoporous organosilica nanoparticles (DMOS-4MPBA) that utilize a single gaseous molecule - hydrogen sulfide (H2S) - as a multifunctional therapeutic agent. DMOS-4MPBA releases H2S selectively within infected microenvironments through glutathione-responsive cleavage of polysulfide bonds. The released H2S concurrently executes three therapeutic mechanisms: disrupting bacterial energy metabolism and membrane integrity, suppressing quorum sensing to inhibit biofilm formation, and promoting immune regulation via macrophage polarization toward the pro-repair M2 phenotype. Both in vitro and in vivo experiments demonstrate strong antibacterial effects, efficient biofilm disruption, and accelerated wound healing, without compromising biosafety. By integrating antibacterial, anti-biofilm, and immunomodulatory capacities into a single H2S-releasing platform, we provide a innovative and potent strategy for treating drug-resistant infections and inflammatory diseases.