SBIR-STTR Award

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. 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.

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase II project is enabling the large-scale manufacturing of a red blood cell membrane coated nanoparticle platform, which was previously demonstrated to be capable of absorbing and neutralizing a wide array of hemolytic pathogenic factors, such as bacterial toxins, animal venoms, and auto-reactive immunoglobulin. Comprised entirely of biocompatible and biodegradable materials and coated by cell membranes derived from natural red blood cells, the nanoparticles are able to circulate for an extended period of time in the circulation. Their biomimetic exterior allows them to serve as a decoy to scavenge virulence factors that attack cell membranes. The nanoformulation may be applied against multiple pressing and unmet medical needs, including animal envenoming, autoimmune hemolytic diseases, and bacterial infections. Successful development of the manufacturing process also has broader impact in the field of nanofabrication and nanomedicine development. The proposed project will enable the red blood cell membrane-coated nanoparticles to be manufactured efficiently and reliably at a large scale toward clinical translation. To ensure that the manufactured nanoformulations will have the optimal size, uniformity, biological activity, and performance, advanced fluidics, filtration, microscopy, and particle tracking techniques will be applied for precision nanoparticle preparation and characterization. Specifically, the proposed research activity will focus on the synthesis of uniform polymeric nanoparticles with consistent physicochemical properties, derivation of purified and undisrupted red blood cell membranes, and reliable cell membrane coating over the nanoparticle substrates. The resulting nanoparticles will be thoroughly examined to iteratively improve the preparation process. Optimized manufacturing protocol will be developed for large-scale production of high quality nanoformulations following good manufacturing practices (GMP). The project will facilitate the bench-to-bedside transition of the novel biomimetic nanoparticle platform, which has significant implications in addressing the many major diseases involving protein toxins.