Lipopolysaccharide hydrolysis-targeting nano-chimeras detoxify endotoxin through specific adsorption and efficient degradation

Lipopolysaccharide (LPS), a potent immunogenic component of the outer membrane of Gram-negative bacteria, triggers severe inflammation and organ failure even at nanomolar concentrations. However, neutralizing LPS in vivo remains challenging due to the high abundance of other biomolecules in biological fluids, which interfere with LPS detoxification. Brassicaceae species produce a transmembrane protein termed lipooligosaccharide-specific reduced elicitation (LORE) that specifically recognizes and binds LPS. Here, we prepare plant-derived nanovesicles naturally presenting LORE on their surface and integrate them with cerium-based nanozymes exhibiting LPS hydrolysis activity. We show that these hybrid nanostructures (Atv@Ce) neutralize LPS through two coordinated mechanisms: LORE captures LPS specifically, while nanozymes chemically degrade the phosphate groups and glycosidic bonds in the lipid A moiety. This dual strategy effectively attenuates both local and systemic inflammation, offering a biocompatible detoxification strategy with translational potential. Our work provides an insight into nanomaterial-mediated detoxification. Detoxifying the immunogenic lipopolysaccharide (LPS) remains challenging. Here, the authors show that the Brassicaceae protein LORE binds LPS with high affinity and develop plant-derived nanovesicles displaying native LORE, combined with cerium-based nanozymes, to enable LPS hydrolysis.