Rapid-releasing of HI-6 brain-targeted mesoporous silica nanoparticles for nerve agent detoxification

The toxic nerve agent (NA) soman is the most toxic artificially synthesized compound that can rapidly penetrate into the brain and irreversibly inhibit acetylcholinesterase (AChE) activity, leading to immediate death. However, there are currently few brain-targeted nanodrugs that can treat acute che...

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Veröffentlicht in:Nanoscale 2016-05, Vol.8 (18), p.9537-9547
Hauptverfasser: Yang, Jun, Fan, Lixue, Wang, Feijian, Luo, Yuan, Sui, Xin, Li, Wanhua, Zhang, Xiaohong, Wang, Yongan
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container_end_page 9547
container_issue 18
container_start_page 9537
container_title Nanoscale
container_volume 8
creator Yang, Jun
Fan, Lixue
Wang, Feijian
Luo, Yuan
Sui, Xin
Li, Wanhua
Zhang, Xiaohong
Wang, Yongan
description The toxic nerve agent (NA) soman is the most toxic artificially synthesized compound that can rapidly penetrate into the brain and irreversibly inhibit acetylcholinesterase (AChE) activity, leading to immediate death. However, there are currently few brain-targeted nanodrugs that can treat acute chemical brain poisoning owing to the limited drug-releasing speed. The present study investigated the effectiveness of a nanodrug against NA toxicity that has high blood-brain barrier penetration and is capable of rapid drug release. Transferrin-modified mesoporous silica nanoparticles (TF-MSNs) were conjugated with the known AChE reactivator HI-6. This nanodrug rapidly penetrated the blood-brain barrier in zebrafish and mice and restored cerebral AChE activity via the released HI-6, preventing the brain damage caused by soman poisoning and increasing the survival rate in mice. Furthermore, there was no toxicity associated with the MSNs in mice or rats. These results demonstrate that TF-MSNs loaded with HI-6 represent the most effective antidote against NA poisoning by soman reported to date, and suggest that MSNs are a safe alternative to conventional drugs and an optimal nanocarrier for treating brain poisoning, which requires acute pulse cerebral administration. Transferrin-modified mesoporous silica nanoparticles could rapidly deliver and release an antidote to the brain for effectively detoxifying nerve agent poisoning.
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title Rapid-releasing of HI-6 brain-targeted mesoporous silica nanoparticles for nerve agent detoxification
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