Fenozyme Protects the Integrity of Blood Brain Barrier against Experimental Cerebral Malaria
Shuai Zhao, Hongxia Duan, Yili Yang, Xiyun Yan and 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 the anti-malaria 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 to BBB endothelial cells (BBB ECs), and 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 liver to 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 anti-malaria drug is a novel strategy for the treatment of cerebral malaria.
附件下载：
Fenozyme Protects the Integrity of Blood Brain Barrier against Experimental Cerebral Malaria, Nano letters, 01 Nov 2019
Nano letters, 01 November, 2019，DOI：https://doi.org/10.1021/acs.nanolett.9b03774
Fenozyme Protects the Integrity of Blood Brain Barrier against Experimental Cerebral Malaria
Shuai Zhao, Hongxia Duan, Yili Yang, Xiyun Yan and 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 the anti-malaria 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 to BBB endothelial cells (BBB ECs), and 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 liver to 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 anti-malaria drug is a novel strategy for the treatment of cerebral malaria.
文章链接：https://pubs.acs.org/doi/10.1021/acs.nanolett.9b03774
相关报道：http://www.ibp.cas.cn/kyjz/zxdt/201911/t20191104_5420434.html