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

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• 作者：Jeffrey O’Brien ; Shih-Hui Lee ; Shunsuke Onogi ; Kenneth J. Shea
• 刊名：Journal of the American Chemical Society
• 出版年：2016
• 出版时间：December 28, 2016
• 年：2016
• 卷：138
• 期：51
• 页码：16604-16607
• 全文大小：314K
• ISSN：1520-5126

文摘

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 PLA₂ over 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.