title: Engineering the Protein Corona of a Synthetic Polymer Nanoparticle for Broad-Spectrum Sequestration and Neutralization of Venomous Biomacromolecules.
abstract: 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 A2(PLA2), 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 PLA2over abundant serum proteins, was not cytotoxic, and showed substantially long dissociation rates from PLA2. These findings suggest that it may show efficacy as an in vivo venom sequestrant and may serve as a generalized lipid-mediated toxin sequestrant.
authors.affiliation: Department of Chemistry, University of California, Irvine , Irvine, California 92697, United States.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: O'Brien
authors.affiliation: Department of Chemistry, University of California, Irvine , Irvine, California 92697, United States.
authors.forename: Shih-Hui
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Chemistry, University of California, Irvine , Irvine, California 92697, United States.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Onogi
authors.affiliation: Department of Chemistry, University of California, Irvine , Irvine, California 92697, United States.
authors.forename: Kenneth J
authors.identifier: 0000-0001-5926-0059
authors.initials: KJ
authors.lastname: Shea
mesh_terms: D004738:Engineering; D005340:Fibrinogen / Q000378:metabolism*; D007700:Kinetics; D053758:Nanoparticles / Q000737:chemistry*; D036103:Nanotechnology; D054467:Phospholipases A2 / Q000737:chemistry* / Q000378:metabolism*; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry*; D000066970:Protein Corona / Q000737:chemistry*; D014688:Venoms / Q000737:chemistry*
chemical_list: D011108:Polymers; D000066970:Protein Corona; D014688:Venoms; D005340:Fibrinogen; D054467:Phospholipases A2