脑疟疾
血脑屏障
伯氏疟原虫
疟疾
过氧化氢酶
医学
中枢神经系统
免疫学
药理学
生物
炎症
恶性疟原虫
氧化应激
内科学
作者
Shuai Zhao,Hongxia Duan,Yili Yang,Xiyun Yan,Kelong Fan
出处
期刊:Nano Letters
[American Chemical Society]
日期:2019-11-01
卷期号:19 (12): 8887-8895
被引量:60
标识
DOI:10.1021/acs.nanolett.9b03774
摘要
Cerebral malaria is a lethal complication of malaria infection characterized by central nervous system dysfunction and is often not effectively treated by antimalarial combination therapies. It has been shown that the sequestration of the parasite-infected red blood cells that interact with cerebral vessel endothelial cells and the damage of the blood-brain barrier (BBB) play critical roles in the pathogenesis. In this study, we developed a ferritin nanozyme (Fenozyme) composed of recombinant human ferritin (HFn) protein shells that specifically target BBB endothelial cells (BBB ECs) and the inner Fe3O4 nanozyme core that exhibits reactive oxygen species-scavenging catalase-like activity. In the experimental cerebral malaria (ECM) mouse model, administration of the Fenozyme, but not HFn, markedly ameliorated the damage of BBB induced by the parasite and improved the survival rate of infected mice significantly. Further investigations found that Fenozyme, as well as HFn, was able to polarize the macrophages in the liver to the M1 phenotype and promote the elimination of malaria in the blood. Thus, the catalase-like activity of the Fenozyme is required for its therapeutic effect in the mouse model. Moreover, the Fenozyme significantly alleviated the brain inflammation and memory impairment in ECM mice that had been treated with artemether, indicating that combining Fenozyme with an antimalarial drug is a novel strategy for the treatment of cerebral malaria.
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