Fenozyme Protects the Integrity of the Blood–Brain Barrier against Experimental Cerebral Malaria
- Shuai ZhaoShuai ZhaoCAS Engineering Laboratory for Nanozyme, Key Laboratory of Protein and Peptide Pharmaceutical, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, ChinaCollege of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, ChinaMore by Shuai Zhao
- Hongxia DuanHongxia DuanCAS Engineering Laboratory for Nanozyme, Key Laboratory of Protein and Peptide Pharmaceutical, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, ChinaMore by Hongxia Duan
- Yili YangYili YangSuzhou Institute of Systems Medicine, Center for Systems Medicine, Chinese Academy of Medicine Sciences, Suzhou 215133, ChinaMore by Yili Yang
- Xiyun Yan*Xiyun Yan*E-mail: [email protected]. Tel: +86 10-64888583. Fax: +86-10-64888584.CAS Engineering Laboratory for Nanozyme, Key Laboratory of Protein and Peptide Pharmaceutical, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, ChinaCollege of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, ChinaJoint Laboratory of Nanozymes in Zhengzhou University, Academy of Medical Sciences, Zhengzhou University, 40 Daxue Road, Zhengzhou 450052, ChinaMore by Xiyun Yan
- Kelong Fan*Kelong Fan*E-mail: [email protected]. Tel: +86-10-64888280. Fax: +86-10-64888584.CAS Engineering Laboratory for Nanozyme, Key Laboratory of Protein and Peptide Pharmaceutical, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, ChinaJoint Laboratory of Nanozymes in Zhengzhou University, Academy of Medical Sciences, Zhengzhou University, 40 Daxue Road, Zhengzhou 450052, ChinaMore by Kelong Fan
Abstract
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.
Cited By
This article is cited by 2 publications.
- Chuang Liu, Yingying Yan, Xiaowei Zhang, Yuanyang Mao, Xianqing Ren, Chaoyuan Hu, Weiwei He, Jun-jin Yin. Regulating the pro- and anti-oxidant capabilities of bimetallic nanozymes for the detection of Fe 2+ and protection of Monascus pigments. Nanoscale 2020, 12 (5) , 3068-3075. DOI: 10.1039/C9NR10135G.
- Yanan Zhang, Yiliang Jin, Haixia Cui, Xiyun Yan, Kelong Fan. Nanozyme-based catalytic theranostics. RSC Advances 2020, 10 (1) , 10-20. DOI: 10.1039/C9RA09021E.