Protective effect of lipoic acid modification on brain dysfunctions of mice induced by mesoporous silica nanoparticles
Protective effect of lipoic acid modification on brain dysfunctions of mice induced by mesoporous silica nanoparticles
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硫辛酸修饰对介孔二氧化硅纳米粒子所致小鼠脑功能障碍的保护作用
DOI：
10.1016/j.cej.2021.128957
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发表时间：
2021-02
影响因子：
15.1
通讯作者：
Chun-Hua Yan
中科院分区：
文献类型：
--
作者：
Ailing Sun;Di Qian;Zheng Wang;Yiliang Xu;Haihong Ye;Chen-Jie Fang;Chun-Hua Yan
介孔二氧化硅纳米粒子（MSN）由于其结构优势而在生物医学领域显示出潜力。然而，人们对其穿越血脑屏障 (BBB) 的能力知之甚少，并且与 MSN 暴露和对应溶液相关的对大脑功能的潜在不利影响仍有待阐明。本研究结果表明，原始MSNs破坏BBB并进入大脑，因此，小鼠的社交能力和认知等大脑功能显着受损。体外研究表明，原始 MSN 通过产生活性氧 (ROS) 抑制细胞增殖，从而导致线粒体功能受损，并通过 JNK 和 p38 MAPK（丝裂原激活蛋白激酶）信号通路激活细胞凋亡。体内研究表明，接触 MSN 会引发氧化应激，激活线粒体凋亡信号通路和 caspase 家族，并导致大脑中的细胞凋亡。暴露于硫辛酸（LA）修饰的MSN（MSN-LA）后，观察到体外和体内损伤的减轻。综合多级毒性评估还表明，由于 LA 的卓越抗氧化特性，LA 的修饰可能会减轻脑功能障碍。
Mesoporous silica nanoparticles (MSNs) have shown potential in biomedicine due to their structural advantages. However, little is known concerning their ability crossing blood-brain barrier (BBB), and potential adverse effects on the brain function associated with MSNs exposure and counterpart solution remains to be elucidated. The findings in the present study indicate that pristine MSNs destroy BBB and enter into the brain, and therefore, the brain functions such as social ability and cognition of the mice is impaired remarkably. Thein vitrostudy indicates that the pristine MSNs inhibit cellular proliferation via generation of reactive oxygen species (ROS), which results in impaired mitochondrial function and activates cellular apoptosis via JNK and p38 MAPK (mitogen-activated protein kinase) signaling pathway. Thein vivostudy demonstrates that exposure to the MSNs triggers oxidative stress, activates mitochondrial apoptosis signaling pathways and the caspase family, and leads to cell apoptosis in the brain. The mitigated damages bothin vitroandin vivoare observed after exposure to lipoic acid (LA) modified MSNs (MSN-LA). The integrated multilevel toxicity assessments also indicate that the brain dysfunction may be mitigated by the modification of LA, due to superior antioxidative property of LA.
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DOI：
10.1053/scnp00100241
发表时间：
1996-10
期刊：
Seminars in clinical neuropsychiatry
影响因子：
--
作者：
Jeffrey L. Cummings;C. Diaz;M. Levy;G. Binetti;I. LitvanI
通讯作者：
Jeffrey L. Cummings;C. Diaz;M. Levy;G. Binetti;I. LitvanI
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影响因子：
29.4
作者：
Wu, Meiying;Meng, Qingshuo;Shi, Jianlin
通讯作者：
Shi, Jianlin
用于程序化肿瘤治疗的刺激响应“集束炸弹”
影响因子：
17.1
作者：
Lei, Qi;Wang, Shi-Bo;Zhang, Xian-Zheng
通讯作者：
Zhang, Xian-Zheng
影响因子：
8.6
作者：
Huh, S;Wiench, JW;Lin, VSY
通讯作者：
Lin, VSY
影响因子：
15
作者：
Lin, Yu-Shen;Haynes, Christy L.
通讯作者：
Haynes, Christy L.