Brain-targeted nanoreactors prevent the development of organophosphate-induced delayed neurological damage.

Humans Organophosphates / metabolism Organophosphate Poisoning / metabolism Brain / metabolism Antidotes / metabolism Nanotechnology
Brain targeting Delayed neurological damage Enzyme immobilization Nanoreactors Organophosphates

Journal

Journal of nanobiotechnology
ISSN: 1477-3155
Titre abrégé: J Nanobiotechnology
Pays: England
ID NLM: 101152208

Informations de publication

Date de publication:
07 Aug 2023
Historique:
received: 18 06 2023
accepted: 31 07 2023
medline: 9 8 2023
pubmed: 8 8 2023
entrez: 7 8 2023
Statut: epublish

Résumé

Organophosphate (OP)-induced delayed neurological damage is attributed to permanent neuropathological lesions caused by irreversible OP-neurocyte interactions, without potent brain-targeted etiological antidotes to date. The development of alternative therapies to achieve intracerebral OP detoxification is urgently needed. We designed a brain-targeted nanoreactor by integrating enzyme immobilization and biomimetic membrane camouflaging protocols with careful characterization, and then examined its blood-brain barrier (BBB) permeability both in vitro and in vivo. Subsequently, the oxidative stress parameters, neuroinflammatory factors, apoptotic proteins and histopathological changes were measured and neurobehavioral tests were performed. The well-characterized nanoreactors exerted favourable BBB penetration capability both in vitro and in vivo, significantly inhibiting OP-induced intracerebral damage. At the cellular and tissue levels, nanoreactors obviously blocked oxidative stress, cellular apoptosis, inflammatory reactions and brain histopathological damage. Furthermore, nanoreactors radically prevented the occurrence of OP-induced delayed cognitive deficits and psychiatric abnormality. The nanoreactors significantly prevented the development of OP-induced delayed neurological damage, suggesting a potential brain-targeted etiological strategy to attenuate OP-related delayed neurological and neurobehavioral disorders.

Sections du résumé

BACKGROUND BACKGROUND
Organophosphate (OP)-induced delayed neurological damage is attributed to permanent neuropathological lesions caused by irreversible OP-neurocyte interactions, without potent brain-targeted etiological antidotes to date. The development of alternative therapies to achieve intracerebral OP detoxification is urgently needed.
METHODS METHODS
We designed a brain-targeted nanoreactor by integrating enzyme immobilization and biomimetic membrane camouflaging protocols with careful characterization, and then examined its blood-brain barrier (BBB) permeability both in vitro and in vivo. Subsequently, the oxidative stress parameters, neuroinflammatory factors, apoptotic proteins and histopathological changes were measured and neurobehavioral tests were performed.
RESULTS RESULTS
The well-characterized nanoreactors exerted favourable BBB penetration capability both in vitro and in vivo, significantly inhibiting OP-induced intracerebral damage. At the cellular and tissue levels, nanoreactors obviously blocked oxidative stress, cellular apoptosis, inflammatory reactions and brain histopathological damage. Furthermore, nanoreactors radically prevented the occurrence of OP-induced delayed cognitive deficits and psychiatric abnormality.
CONCLUSION CONCLUSIONS
The nanoreactors significantly prevented the development of OP-induced delayed neurological damage, suggesting a potential brain-targeted etiological strategy to attenuate OP-related delayed neurological and neurobehavioral disorders.

Identifiants

DOI: 10.1186/s12951-023-02039-2 PMID: 37550745 PMC: PMC10405429
pubmed: 37550745
doi: 10.1186/s12951-023-02039-2
pii: 10.1186/s12951-023-02039-2
pmc: PMC10405429
doi:

Substances chimiques

Organophosphates 0
Antidotes 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

256

Subventions

Organisme : National Natural Science Foundation of China
ID : 81974496

Informations de copyright

© 2023. BioMed Central Ltd., part of Springer Nature.

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Auteurs

Shuaijun Zou (S)

Department of Marine Biomedicine and Polar Medicine, Naval Special Medical Centre, Naval Medical University, Shanghai, 200433, China.

Qianqian Wang (Q)

Department of Marine Biomedicine and Polar Medicine, Naval Special Medical Centre, Naval Medical University, Shanghai, 200433, China.

Qian He (Q)

The Third Affiliated Hospital, Naval Medical University, Shanghai, 200433, China.

Guoyan Liu (G)

Department of Marine Biomedicine and Polar Medicine, Naval Special Medical Centre, Naval Medical University, Shanghai, 200433, China.

Juxingsi Song (J)

Department of Marine Biomedicine and Polar Medicine, Naval Special Medical Centre, Naval Medical University, Shanghai, 200433, China.

Jie Li (J)

Department of Marine Biomedicine and Polar Medicine, Naval Special Medical Centre, Naval Medical University, Shanghai, 200433, China.

Fan Wang (F)

Department of Marine Biomedicine and Polar Medicine, Naval Special Medical Centre, Naval Medical University, Shanghai, 200433, China.

Yichao Huang (Y)

Department of Marine Biomedicine and Polar Medicine, Naval Special Medical Centre, Naval Medical University, Shanghai, 200433, China.

Yanan Hu (Y)

Department of Marine Biomedicine and Polar Medicine, Naval Special Medical Centre, Naval Medical University, Shanghai, 200433, China.

Dayuan Zhou (D)

Department of Marine Biomedicine and Polar Medicine, Naval Special Medical Centre, Naval Medical University, Shanghai, 200433, China.

Yongfei Lv (Y)

Department of Marine Biomedicine and Polar Medicine, Naval Special Medical Centre, Naval Medical University, Shanghai, 200433, China.

Yuanjie Zhu (Y)

Department of Marine Biological Injury and Dermatology, Naval Special Medical Centre, Naval Medical University, Shanghai, 200052, China. 13918338960@126.com.

Beilei Wang (B)

Department of Marine Biomedicine and Polar Medicine, Naval Special Medical Centre, Naval Medical University, Shanghai, 200433, China. beileiwang@smmu.edu.cn.

Liming Zhang (L)

Department of Marine Biomedicine and Polar Medicine, Naval Special Medical Centre, Naval Medical University, Shanghai, 200433, China. lmzhang@smmu.edu.cn.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Brain-targeted nanoreactors prevent the...
questionsmedicales.fr › Composés chimiques organiques › Composés organiques du phosphore › Organophosphates › Brain-targeted nanoreactors prevent the...
questionsmedicales.fr › Troubles dus à des produits chimiques › Intoxication › Intoxication aux organophosphates › Brain-targeted nanoreactors prevent the...
questionsmedicales.fr › Système nerveux › Système nerveux central › Encéphale › Brain-targeted nanoreactors prevent the...
questionsmedicales.fr › Actions chimiques et utilisations › Utilisations spécialisées de produits chimiques › Agents protecteurs › Antidotes › Brain-targeted nanoreactors prevent the...
questionsmedicales.fr › Technologie, industrie et agriculture › Technologie › Miniaturisation › Nanotechnologie › Brain-targeted nanoreactors prevent the...