Intelligent lesion blood-brain barrier targeting nano-missiles for Alzheimer's disease treatment by anti-neuroinflammation and neuroprotection.
Intelligent lesion blood-brain barrier targeting nano-missiles for Alzheimer's disease treatment by anti-neuroinflammation and neuroprotection.
复制标题
智能病变血脑屏障靶向纳米导弹通过抗神经炎症和神经保护治疗阿尔茨海默病
DOI：
10.1016/j.apsb.2022.02.001
复制
发表时间：
2022-04
影响因子：
14.5
通讯作者：
Gao, Huile
中科院分区：
文献类型：
--
作者：
He, Xueqin;Wang, Xiaorong;Yang, Lianyi;Yang, Zhihang;Yu, Wenqi;Wang, Yazhen;Liu, Rui;Chen, Meiwan;Gao, Huile
关键词：
阿尔茨海默病（AD）的治疗是神经退行性疾病中最困难的挑战之一，因为血脑屏障（BBB）渗透性不足和药物在脑内分布不理想。因此，我们建立了一个ibuprofen和FK506包封药物共递送系统（ibu&FK@RNPs），该系统可以靶向晚期糖基化终末产物受体（RAGE），并对AD中高水平的活性氧（ROS）做出反应。RAGE在AD病变神经血管单元上高度特异性表达，这一特性有助于提高系统的靶向特异性，减少正常脑内的非选择性分布。同时，这两种药物可以在AD病变的星形细胞中特异性释放，以响应高水平的ROS。结果，AD小鼠的认知能力明显改善，a β斑块数量减少。神经毒性也随着神经元的结构再生和功能恢复而减轻。此外，以NF-κB通路为主导的神经炎症明显受到抑制，脑组织中NF-κB和IL-1β水平下降。综上所述，Ibu&FK@RNPs可以有效且连续地靶向AD病变的血脑屏障和星形胶质细胞。从而显著增强脑内药物蓄积，通过抗神经炎症和保护神经有效治疗AD。制备了ibu&FK@RNPs的活性氧（ROS）反应性编程受体（RAGE）靶向递送库，通过抗神经炎症和神经保护作用于星形胶质细胞和神经元，治疗阿尔茨海默病（AD）。
The treatment of Alzheimer's disease (AD) is one of the most difficult challenges in neurodegenerative diseases due to the insufficient blood‒brain barrier (BBB) permeability and unsatisfactory intra-brain distribution of drugs. Therefore, we established an ibuprofen and FK506 encapsulated drug co-delivery system (Ibu&FK@RNPs), which can target the receptor of advanced glycation endproducts (RAGE) and response to the high level of reactive oxygen species (ROS) in AD. RAGE is highly and specifically expressed on the lesion neurovascular unit of AD, this property helps to improve targeting specificity of the system and reduce unselective distribution in normal brain. Meanwhile, these two drugs can be specifically released in astrocytes of AD lesion in response to high levels of ROS. As a result, the cognition of AD mice was significantly improved and the quantity of Aβ plaques was decreased. Neurotoxicity was also alleviated with structural regeneration and functional recovery of neurons. Besides, the neuroinflammation dominated by NF-κB pathway was significantly inhibited with decreased NF-κB and IL-1β in the brain. Overall, Ibu&FK@RNPs can efficiently and successively target diseased BBB and astrocytes in AD lesion. Thus it significantly enhances intracephalic accumulation of drugs and efficiently treats AD by anti-neuroinflammation and neuroprotection. Reactive oxygen species (ROS)-responsive programmed receptor of advanced glycation endproducts (RAGE) targeted delivery depot of Ibu&FK@RNPs was prepared to act on astrocytes and neurons in the treatment of Alzheimer's disease (AD) through anti-neuroinflammation and neuroprotection.
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影响因子：
8.8
作者：
Friker LL;Scheiblich H;Hochheiser IV;Brinkschulte R;Riedel D;Latz E;Geyer M;Heneka MT
通讯作者：
Heneka MT
影响因子：
14
作者：
通讯作者：
--
DOI：
10.1002/trc2.12050
发表时间：
2020-01-01
影响因子：
4.8
作者：
Cummings, Jeffrey;Lee, Garam;Zhong, Kate
通讯作者：
Zhong, Kate
DOI：
10.1158/1078-0432.ccr-12-0221
发表时间：
2012-08-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Arumugam T;Ramachandran V;Gomez SB;Schmidt AM;Logsdon CD
通讯作者：
Logsdon CD
Endo/溶酶体逃逸递送库可改善 BBB 转胞吞作用和阿尔茨海默病的神经元靶向治疗
影响因子：
19
作者：
Cai, Lulu;Yang, Chuanyao;Gao, Huile
通讯作者：
Gao, Huile