This Small Business Innovation Research (SBIR) Phase I project will develop a cholesterol-enriched biomimetic toxin nanopsonges with enhanced toxin-binding affinity for efficient scavenging of cytolytic toxins in the bloodstream. Consisting of nanoparticle-supported red blood cell membranes, toxin nanosponges serve as a biomimetic decoy to arrest and neutralize pore-forming toxins regardless of their molecular structures. The platform can detoxify alpha-hemolysin, a major toxin in methicillin-resistant Staphylococcus aureus (MRSA), as well as other toxin types with different molecular structures. Toward translating the platform to treatment of toxin-induced injuries and diseases, this Phase I project aims to enhance the toxin-binding affinity of the nanosponges for more efficient toxin removal by enriching the platform with cholesterol, a common receptor for many pore-forming toxins. The project also serves to expand the toxin nanosponge platform from the existing mouse blood model to two other non-human animal species, rat and pig. <br/><br/><br/>The broader impact/commercial potential of this project lies in the unique biomimetic properties of the nanosponges and its broad applicability against multiple pore-forming toxin types. The platform possesses significant therapeutic potential owing to broad presence of membrane-damaging virulence factors in bacteria and in animal venoms. In addition, the platform presents a unique nanostructure that elegantly bridges biological materials with synthetic nanomaterials. The success of the project will bring forth a potent therapeutic option against many virulence factors and establish a new class of nanoparticulate for emerging biomedical applications. This program will benefit the field of antitoxin treatment as well as nanotechnology studies in general.