Engineering the Protein Corona of a Synthetic Polymer Nanoparticle for Broad-Spectrum Sequestration and Neutralization of Venomous Biomacromolecules

Biochemical diversity of venom extracts often occurs within a small number of shared protein families. Developing a sequestrant capable of broad-spectrum neutralization across various protein isoforms within these protein families is a necessary step in creating broad-spectrum antivenom. Using directed synthetic evolution to optimize a nanoparticle (NP) formulation capable of sequestering and neutralizing venomous phospholipase A 2 (PLA 2 ), we demonstrate that broad-spectrum neutralization and sequestration of venomous biomacromolecules is possible via a single optimized NP formulation. Furthermore, this optimized NP showed selectivity for venomous PLA 2 over abundant serum proteins, was not cytotoxic, and showed substantially long dissociation rates from PLA 2 . These findings suggest that it may show efficacy as an in vivo venom sequestrant and may serve as a generalized lipid-mediated toxin sequestrant.