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脑靶向纳米反应器可预防有机磷诱导的迟发性神经损伤。

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

机构信息

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

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

出版信息

J Nanobiotechnology. 2023 Aug 7;21(1):256. doi: 10.1186/s12951-023-02039-2.

DOI:10.1186/s12951-023-02039-2
PMID:37550745
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10405429/
Abstract

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

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

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

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.

摘要

背景

有机磷（OP）诱导的迟发性神经损伤归因于不可逆的 OP-神经细胞相互作用引起的永久性神经病理学损伤，目前尚无有效的针对大脑的病因解毒剂。迫切需要开发替代疗法以实现颅内 OP 解毒。

方法

我们通过整合酶固定化和仿生膜伪装方案设计了一种脑靶向纳米反应器，并进行了仔细的表征，然后在体外和体内研究了其血脑屏障（BBB）通透性。随后，测量了氧化应激参数、神经炎症因子、凋亡蛋白和组织病理学变化，并进行了神经行为学测试。

结果

经过良好表征的纳米反应器在体外和体内均表现出良好的 BBB 穿透能力，显著抑制了 OP 诱导的颅内损伤。在细胞和组织水平上，纳米反应器明显阻断了氧化应激、细胞凋亡、炎症反应和脑组织病理学损伤。此外，纳米反应器从根本上防止了 OP 诱导的迟发性认知功能障碍和精神异常的发生。

结论

纳米反应器显著预防了 OP 诱导的迟发性神经损伤的发生，提示了一种潜在的针对大脑的病因治疗策略，以减轻 OP 相关的迟发性神经和神经行为障碍。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c520/10405429/5176f4d8e304/12951_2023_2039_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c520/10405429/ba622f62b715/12951_2023_2039_Sch1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c520/10405429/7a0cf46890c5/12951_2023_2039_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c520/10405429/1199a1b32b9d/12951_2023_2039_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c520/10405429/b392f9e872a5/12951_2023_2039_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c520/10405429/0bbc7a31ef4c/12951_2023_2039_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c520/10405429/bee4f398ca1f/12951_2023_2039_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c520/10405429/0d69c89d3633/12951_2023_2039_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c520/10405429/5176f4d8e304/12951_2023_2039_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c520/10405429/ba622f62b715/12951_2023_2039_Sch1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c520/10405429/7a0cf46890c5/12951_2023_2039_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c520/10405429/1199a1b32b9d/12951_2023_2039_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c520/10405429/b392f9e872a5/12951_2023_2039_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c520/10405429/0bbc7a31ef4c/12951_2023_2039_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c520/10405429/bee4f398ca1f/12951_2023_2039_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c520/10405429/0d69c89d3633/12951_2023_2039_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c520/10405429/5176f4d8e304/12951_2023_2039_Fig7_HTML.jpg

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