Perfluorocarbon Nanoparticles Incorporating Ginkgolide B: Artificial O2 Carriers with Antioxidant Activity and Antithrombotic Effect

载银杏内酯B的全氟碳纳米粒子:具有抗氧化活性和抗血栓作用的人工O2载体

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作者:Wei Meng, Hongbo Ye, Zhifang Ma, Lei Liu, Tianci Zhang, Qiaoyi Han, Zehong Xiang, Yu Xia, Yue Ke, Xinghua Guan, Qiang Shi, Fazly I Ataullakhanov, Mikhail Panteleev

Abstract

Ischemic stroke primarily leads to insufficient oxygen delivery in ischemic area. Prompt reperfusion treatment for restoration of oxygen is clinically suggested but mediates more surging reactive oxygen species (ROS) generation and oxidative damage, known as ischemia-reperfusion injury (IRI). Therefore, the regulation of oxygen content is a critical point to prevent cerebral ischemia induced pathological responses and simultaneously alleviate IRI triggered by the sudden oxygen restoration. In this work, we constructed a perfluorocarbon (PFC)-based artificial oxygen nanocarrier (PFTBA-L@GB), using an ultrasound-assisted emulsification method, alleviates the intracerebral hypoxic state in ischemia stage and IRI after reperfusion. The high oxygen solubility of PFC allows high oxygen efficacy. Furthermore, PFC has the adhesion affinity to platelets and prevents the overactivation of platelet. The encapsulated payload, ginkgolide B (GB) exerts its anti-thrombosis by antagonism on platelet activating factor and antioxidant effect by upregulation of antioxidant molecular pathway. The versatility of the present strategy provides a practical approach to build a simple, safe, and relatively effective oxygen delivery agent to alleviate hypoxia, promote intracerebral oxygenation, anti-inflammatory, reduce intracerebral oxidative stress damage and thrombosis and caused by stroke.

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