Design, Synthesis and Characterization of Superparamagnetic Nanoparticles Conjugated with 2-Pyridinium Aldoxime as Potential Antidotes of Nerve Agents

Background and Aim: Organophosphate compounds, including nerve agents, pesticides, chemical agent analogs, and Novichok, pose a serious health hazard to humans. Their use against humans was banned by 192 countries in 1993 under the Chemical Weapons Convention. The toxic effects of these compounds involve the phosphorylation and subsequent inhibition of the enzyme acetylcholinesterase, leading to the accumulation of acetylcholine in the synapses of the central and peripheral nervous systems, resulting in neurotoxic poisoning symptoms. The drugs used to treat this poisoning are compounds that can cross the blood-brain barrier by a maximum of 10% and therefore do not effectively detoxify the central nervous system. This research aims to design and synthesize a superparamagnetic nano-reactivator to activate the inhibited enzyme in the central nervous system.
Methods: In this study, iron oxide nanoparticles conjugated with 2-pyridinium aldoxime were designed and synthesized in four steps. The characteristics of the nanoparticles were determined by infrared spectroscopy, energy-dispersive X-ray spectroscopy (EDS), elemental analysis, dynamic light scattering (DLS), and electron microscopy (SEM). Their activation effect was compared with pralidoxime, a commercially available drug, using the Ellman method in vitro.
Results: The results of the Ellman method showed that the percentage of activation of the paraoxon-inhibited enzyme by pralidoxime as a commercially available antidote and the synthesized nanoparticles at a concentration of 5 mM over 30 minutes was 88.6% and 39.3%, respectively.
Conclusion: This study demonstrated that the designed iron oxide nanoparticles conjugated with 2-pyridinium aldoxime can be synthesized and activate acetylcholinesterase inhibited by paraoxon. Therefore, future studies should investigate the effect of other groups such as 4-pyridinium aldoxime, 2,4-pyridinium aldoxime, etc., on the enzyme activation performance and the ability of these nanoparticles to cross the blood-brain barrier.