用凝血酶納米粒子來治療內出血

論文標題：Thrombin@Fe3O4 nanoparticles for use as a hemostatic agent in internal bleeding

作者：Emiliya M. Shabanova, Andrey S. Drozdov, Anna F. Fakhardo, Ivan P. Dudanov, Marina S. Kovalchuk, Vladimir V. Vinogradov

數字識別碼：10.1038/s41598-017-18665-4

原文鏈接：

出血是導致過早死亡的主要因素之一，而內出血是其中最危險的出血類型。

近日，在《科學報告》發表的一篇名為Thrombin@ Fe3O4 nanoparticles for use as a hemostatic agent in internal bleeding的文章里，來自俄羅斯聖彼得堡國立信息技術機械與光學大學的Vladimir V. Vinogradov 的團隊第一次使用止血磁性納米顆粒來進行內出血微創治療，即將納米顆粒直接導入循環系統，然後利用外加磁場來定位流血區域。納米顆粒的製備是通過將人凝血酶（THR）包埋到由溶膠-凝膠法製備的磁鐵礦結構中，然後研磨至200nm以下，最後進行膠體化。製成的膠體在體外實驗環境下，展現了凝血效果，引起了血漿的凝固。

Vinogradov 的團隊還利用血管模型展示了，凝血酶@鐵化合物因為活性較低，不會引起系統性血栓形成，但如果施加外加磁場使其聚集，同時注射纖維蛋白原，則會加速局部止血速度。作者使用帶有穿孔的血管模型，穿孔區域有循環血液流動，施加了永久磁場之後，止血速度是對比組的6.5倍。作者還對樣品進行了生物相容性實驗，HELF 和HeLa細胞均未展現毒性效應。

圖1：不同實驗組凝血時間和失血量對比圖。

摘要：Bleeding remains one of the main causes of premature mortality at present, with internal bleeding being the most dangerous case. In this paper, magnetic hemostatic nanoparticles are shown for the first time to assist in minimally invasive treatment of internal bleeding, implying the introduction directly into the circulatory system followed by localization in the bleeding zone due to the application of an external magnetic field. Nanoparticles were produced by entrapping human thrombin (THR) into a sol-gel derived magnetite matrix followed by grinding to sizes below 200 nm and subsequent colloidization. Prepared colloids show protrombotic activity and cause plasma coagulation in in vitro experiments. We also show here using a model blood vessel that the THR@ferria composite does not cause systematic thrombosis due to low activity, but being concentrated by an external magnetic field with simultaneous fibrinogen injection accelerates local hemostasis and stops the bleeding. For instance, a model vessel system with circulating blood at the puncture of the vessel wall and the application of a permanent magnetic field yielded a hemostasis time by a factor of 6.5 shorter than that observed for the control sample. Biocompatibility of composites was tested on HELF and HeLa cells and revealed no toxic effects.

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期刊介紹：Scientific Reports(https://www.nature.com/srep/) is an online, open access journal from the publishers of Nature. We publish scientifically valid primary research from all areas of the natural and clinical sciences.

The 2017 journal metrics for Scientific Reports are as follows:

?2-year impact factor: 4.122

?5-year impact factor: 4.609

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?2-year Median: 2

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