Brain-targeted nanoreactors prevent the development of organophosphate-induced delayed neurological damage.
Brain-targeted nanoreactors prevent the development of organophosphate-induced delayed neurological damage.
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DOI：
10.1186/s12951-023-02039-2
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发表时间：
2023-08-07
影响因子：
10.2
通讯作者：
Zhang, Liming
中科院分区：
文献类型：
--
作者：
Zou, Shuaijun;Wang, Qianqian;He, Qian;Liu, Guoyan;Song, Juxingsi;Li, Jie;Wang, Fan;Huang, Yichao;Hu, Yanan;Zhou, Dayuan;Lv, Yongfei;Zhu, Yuanjie;Wang, Beilei;Zhang, Liming
有机磷（OP）诱导的迟发性神经损伤是由于不可逆的OP-神经细胞相互作用引起的永久性神经病理学病变，迄今为止没有有效的脑靶向病原学解毒剂。迫切需要开发替代疗法来实现脑内OP解毒。我们设计了一个脑靶向纳米反应器，通过整合酶固定化和仿生膜包埋方案与仔细的表征，然后在体外和体内检测其血脑屏障（BBB）的通透性。随后，测定氧化应激参数、神经炎症因子、凋亡蛋白和组织病理学变化，并进行神经行为测试。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OP诱导的脑内损伤。在细胞和组织水平，纳米反应器明显阻断氧化应激、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诱导的延迟性认知缺陷和精神异常的发生。纳米反应器显着防止OP诱导的迟发性神经损伤的发展，这表明一种潜在的脑靶向病因学策略，以减轻OP相关的迟发性神经和神经行为障碍。在线版本包含补充材料，可通过10.1186/s12951-023-02039-2获得。
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. The online version contains supplementary material available at 10.1186/s12951-023-02039-2.
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影响因子：
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作者：
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影响因子：
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通讯作者：
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