Engineered nanoparticles bind elapid snake venom toxins and inhibit venom-induced dermonecrosis

• Published in: PLoS neglected tropical diseases 2018-10, Vol.12 (10), p.e0006736
• Main Authors: O'Brien, Jeffrey, Lee, Shih-Hui, Gutiérrez, José María, Shea, Kenneth J
• Format: Article
• Language: English
• Subjects: Animals; Antivenom; Biology and Life Sciences; Chemistry; Cytotoxicity; Damage; Disease Models, Animal; Elapid Venoms - metabolism; Elapidae; Engineering and Technology; Epitopes; Global health; Hydrogel, Polyethylene Glycol Dimethacrylate - metabolism; Hydrogels; Immunization; Immunoglobulins; Immunology; Isoforms; Medicine and Health Sciences; Mice; Naja; Nanoparticles; Nanoparticles - metabolism; Necrosis - prevention & control; Phospholipase A2; Protein Binding; Proteins; Skin Diseases - prevention & control; Snake bites; Snake Bites - complications; Snakes; Therapy; Tissue; Toxins; Toxins, Biological - metabolism; Tropical diseases; Venom; Venom toxins
• ISSN: 1935-2735; 1935-2727; 1935-2735
• DOI: 10.1371/journal.pntd.0006736

Envenomings by snakebites constitute a serious and challenging global health issue. The mainstay in the therapy of snakebite envenomings is the parenteral administration of animal-derived antivenoms. Significantly, antivenoms are only partially effective in the control of local tissue damage. A novel approach to mitigate the progression of local tissue damage that could complement the antivenom therapy of envenomings is proposed. We describe an abiotic hydrogel nanoparticle engineered to bind to and modulate the activity of a diverse array of PLA2 and 3FTX isoforms found in Elapidae snake venoms. These two families of protein toxins share features that are associated with their common (membrane) targets, allowing for nanoparticle sequestration by a mechanism that differs from immunological (epitope) selection. The nanoparticles are non-toxic in mice and inhibit dose-dependently the dermonecrotic activity of Naja nigricollis venom.