Active protein-capturing hydrogel for broad-spectrum pathogen defense.

Abstract

Proteinaceous agents, including viral particles and allergenic proteins, play central roles in infection, inflammation, and immune dysregulation, yet few materials can broadly neutralize them through direct protein capture. Here, we present an inhalable protein trap (IPT), an active hydrogel that rapidly immobilizes diverse amine-containing biomolecules via NHS-amine chemistry. Structural optimization enables IPT to stably incorporate a high density of reactive NHS esters that remain functional under physiological conditions, allowing efficient protein capture at mucosal surfaces. Upon hydration, powdery IPT rapidly forms an active barrier that covalently traps proteins and proteinaceous particles within minutes. This nonselective capture mechanism allows IPT to bind viral particles, allergens released from pollen or fungi, and soluble immune mediators such as histamine. Across multiple animal models, including allergic rhinitis, pollen-induced allergy, and viral infection, IPT consistently outperformed commercial barrier sprays in blocking pathogenic proteins and mitigating disease progression. These results establish IPT as a versatile platform for broad-spectrum protection at biological interfaces.