Nanodiamond Mediated Delivery of Pyridinium Oxime Antidotes to Central Nervous System for Potential Treatment of Exposure to Nerve Agents

Abstract

Currently available antidotes against toxic organophosphorus compounds suffer from poor permeability across the blood-brain barrier (BBB) and due to this, are limited in their ability to restore the inhibited acetylcholinesterase (AChE) in the central nervous system (CNS). We designed functionalized detonation nanodiamond nanocarrier platforms to transport quaternary oxime antidotes into CNS. We showed that the nanodiamonds with covalently attached 4-oximinopyridinium moiety, cross the layer of Madin-Darby Canine Kidney (MDCK) cells, the surrogate BBB model, and demonstrate a dose-independent reactivation in vitro towards human AChE inhibited by nerve agents GB and VX, and pesticide paraoxon. Confocal microscopy visualization of tight junctions and actin cytoskeleton in MDCK and Human Umbilical Vein Endothelial Cells (HUVEC) revealed temporary disruption of tight junctions at higher nanoparticle concentrations without compromising cell viability or cytoskeletal integrity. Although reactivation was modest, the nanodiamond platform showed promise for delivering quaternary oxime to the central nervous system (CNS) in vitro. The results reveal the potential of detonation nanodiamonds as a promising delivery platform for charged therapeutic agents to CNS aimed to enhance treatment outcomes in organophosphorus poisoning.

Department(s)

Chemistry

Comments

National Eye Institute, Grant G5565

Keywords and Phrases

Acetylcholinesterase reactivators; Blood-brain barrier; Central nervous system; Nanodiamonds; Organophosphorus toxicants; Oximes

International Standard Serial Number (ISSN)

1872-7786; 0009-2797

Document Type

Article - Journal

Document Version

Citation

File Type

text

Language(s)

English

Rights

© 2025 Elsevier, All rights reserved.

Publication Date

22 Oct 2025

PubMed ID

40825460

Link to Full Text

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