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Final manuscript - Nanoparticle-induced enhancement of cholinesterase.docx (4.38 MB)

Nanoparticle-induced enhancement of cholinesterase activity in the presence of malathion: A potential nerve agent therapeutic

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journal contribution
posted on 2023-01-31, 11:36 authored by T Cowen, TS Bedwell, EV Piletska, H Rice, SA Piletsky
Organophosphate nerve agents are associated with assassination, terrorism and chemical warfare, but there has been slow progress in developing a broad-spectrum response to poisoning. For some nerve agents the oxime component of the therapy may not be effective, limiting the effectiveness of emergency treatment that is desperately needed. An alternative therapy may be possible based on accelerating enzyme (acetylcholinesterase) catalysis in unaffected adjacent enzymes. Herein we demonstrate a restoration of acetylcholinesterase activity in malathion-inhibited cell membrane preparations by the administration of functional nanoparticles. The molecularly imprinted polymer nanoparticles were designed to bind selectively to designated enzyme epitopes. Enzyme activity of membrane-bound acetylcholinesterase was measured in the presence of the organophosphate malathion and the selected nanoparticles. Enzymatic acceleration of the cholinesterase was observed at 162 ± 17 % the rate of erythrocyte ghosts without bound nanoparticles. This may restore sufficient acetylcholine hydrolysis to mitigate the effects of poisoning, offsetting the acetylcholine accumulation resulting from enzyme inhibition.

Funding

Ministry of Defence’s Defence and Security Accelerator (DASA)

History

Author affiliation

Department of Chemistry, University of Leicester

Version

  • AM (Accepted Manuscript)

Published in

International Journal of Pharmaceutics

Volume

629

Pagination

122406

Publisher

Elsevier BV

issn

0378-5173

eissn

1873-3476

Copyright date

2022

Available date

2023-11-14

Spatial coverage

Netherlands

Language

eng