title: Butyrylcholinesterase nanocapsule as a long circulating bioscavenger with reduced immune response.
abstract: Butyrylcholinesterase (BChE) is the most promising bioscavenger candidate to treat or prevent organophosphate (OP) poisoning. However, the clinical application of BChE is limited by two obstacles: an inadequate circulation half-life and limited sources for production. Although several modification technologies including glycosylation and PEGylation have been developed to improve its pharmacokinetics, none of them have been able to outperform blood-derived native BChE. In this work, we designed a long-circulating bioscavenger nanogel by coating equine serum-derived BChE with a zwitterionic polymer gel layer. This zwitterionic gel coating protected BChE from denaturation and degradation under harsh conditions. Notably, the nanocapsule exhibited a long circulation half-life of ~45h, a three-fold increase from the unmodified native version, enabling both therapeutic and prophylactic applications. In addition, the gel coating reduced the immunogenicity of equine BChE, unlocking the possibility to use non-human derived BChE as an OP bioscavenger in humans.
authors.affiliation: Department of Chemical Engineering, University of Washington, Seattle, WA 98195, United States.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Chemical Engineering, University of Washington, Seattle, WA 98195, United States.
authors.forename: Priyesh
authors.initials: P
authors.lastname: Jain
authors.affiliation: Department of Chemical Engineering, University of Washington, Seattle, WA 98195, United States.
authors.forename: Caroline
authors.initials: C
authors.lastname: Tsao
authors.affiliation: Department of Chemical Engineering, University of Washington, Seattle, WA 98195, United States.
authors.forename: Andrew
authors.initials: A
authors.lastname: Sinclair
authors.affiliation: Department of Chemical Engineering, University of Washington, Seattle, WA 98195, United States.
authors.forename: Fang
authors.initials: F
authors.lastname: Sun
authors.affiliation: Department of Chemical Engineering, University of Washington, Seattle, WA 98195, United States.
authors.forename: Hsiang-Chieh
authors.initials: HC
authors.lastname: Hung
authors.affiliation: Department of Chemical Engineering, University of Washington, Seattle, WA 98195, United States.
authors.forename: Tao
authors.initials: T
authors.lastname: Bai
authors.affiliation: Department of Chemical Engineering, University of Washington, Seattle, WA 98195, United States.
authors.forename: Kan
authors.initials: K
authors.lastname: Wu
authors.affiliation: Department of Chemical Engineering, University of Washington, Seattle, WA 98195, United States. Electronic address: sjiang@uw.edu.
authors.forename: Shaoyi
authors.initials: S
authors.lastname: Jiang
mesh_terms: D000818:Animals; D001622:Betaine / Q000031:analogs & derivatives* / Q000737:chemistry*; D002091:Butyrylcholinesterase / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D002470:Cell Survival / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000737:chemistry; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D005782:Gels; D006736:Horses; D008297:Male; D051379:Mice; D041681:NIH 3T3 Cells; D053769:Nanocapsules / Q000008:administration & dosage* / Q000737:chemistry; D010261:Paraoxon / Q000031:analogs & derivatives / Q000737:chemistry; D017207:Rats, Sprague-Dawley
chemical_list: D002800:Cholinesterase Inhibitors; D005456:Fluorescent Dyes; D005782:Gels; D053769:Nanocapsules; C121104:ethylparaoxon; D001622:Betaine; D002091:Butyrylcholinesterase; D016650:Fluorescein-5-isothiocyanate; D010261:Paraoxon
keywords: Butyrylcholinesterase; Circulation; Immune response; Nanogel; Organophosphate; Protein delivery