Nanodiamond mediated delivery of pyridinium oxime antidotes to central nervous system for potential treatment of exposure to nerve agents
Identifikátory výsledku
Kód výsledku v IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00179906%3A_____%2F25%3A10503484" target="_blank" >RIV/00179906:_____/25:10503484 - isvavai.cz</a>
Nalezeny alternativní kódy
RIV/60162694:G44__/26:00565922 RIV/62690094:18450/25:50022563
Výsledek na webu
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=bN~dap7iyC" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=bN~dap7iyC</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.cbi.2025.111711" target="_blank" >10.1016/j.cbi.2025.111711</a>
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
Nanodiamond mediated delivery of pyridinium oxime antidotes to central nervous system for potential treatment of exposure to nerve agents
Popis výsledku v původním jazyce
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.
Název v anglickém jazyce
Nanodiamond mediated delivery of pyridinium oxime antidotes to central nervous system for potential treatment of exposure to nerve agents
Popis výsledku anglicky
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.
Klasifikace
Druh
J<sub>imp</sub> - Článek v periodiku v databázi Web of Science
CEP obor
—
OECD FORD obor
30104 - Pharmacology and pharmacy
Návaznosti výsledku
Projekt
<a href="/cs/project/GA22-12859S" target="_blank" >GA22-12859S: Nervově paralytické látky ze skupiny novičoků - toxicita a léčba</a><br>
Návaznosti
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Ostatní
Rok uplatnění
2025
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
Chemico-Biological Interactions
ISSN
0009-2797
e-ISSN
1872-7786
Svazek periodika
420
Číslo periodika v rámci svazku
OCT
Stát vydavatele periodika
NL - Nizozemsko
Počet stran výsledku
12
Strana od-do
111711
Kód UT WoS článku
001563384000001
EID výsledku v databázi Scopus
2-s2.0-105014024159