阿加曲班
血栓
抗血栓
药理学
血小板活化
血小板
化学
血栓形成
生物物理学
纳米医学
膜
活性氧
体内
癌症研究
纳米颗粒
材料科学
医学
纳米技术
凝血酶
外科
免疫学
内科学
作者
Yi Zhao,Ruosen Xie,Nisakorn Yodsanit,Mingzhou Ye,Yuyuan Wang,Bowen Wang,Lian-Wang Guo,K. Craig Kent,Shaoqin Gong
出处
期刊:Biomaterials Science
[The Royal Society of Chemistry]
日期:2021-04-07
卷期号:9 (7): 2696-2708
被引量:14
摘要
Occlusion of blood vessels caused by thrombi is the major pathogenesis of various catastrophic cardiovascular diseases. Thrombi can be prevented or treated by antithrombotic drugs. However, free antithrombotic drugs often have relatively low therapeutic efficacy due to a number of limitations such as short half-life, unexpected bleeding complications, low thrombus targeting capability, and negligible hydrogen peroxide (H2O2)-scavenging ability. Inspired by the abundance of H2O2 and the active thrombus-targeting property of platelets, a H2O2-responsive platelet membrane-cloaked argatroban-loaded polymeric nanoparticle (PNPArg) was developed for thrombus therapy. Poly(vanillyl alcohol-co-oxalate) (PVAX), a H2O2-degradable polymer, was synthesized to form an argatroban-loaded nanocore, which was further coated with platelet membrane. The PNPArg can effectively target the blood clots due to the thrombus-homing property of the cloaked platelet membrane, and subsequently exert combined H2O2-scavenging effect via the H2O2-degradable nanocarrier polymer and antithrombotic effect via argatroban, the released payload. The PNPArg effectively scavenged H2O2 and protected cells from H2O2-induced cellular injury in RAW 264.7 cells and HUVECs. The PNPArg rapidly targeted the thrombosed vessels and remarkably suppressed thrombus formation, and the levels of H2O2 and inflammatory cytokines in the ferric chloride-induced carotid arterial thrombosis mouse model. Safety assessment indicated good biocompatibility of the PNPArg. Taken together, the biomimetic PNPArg offers multiple functionalities including thrombus-targeting, antioxidation, and H2O2-stimulated antithrombotic action, thereby making it a promising therapeutic nanomedicine for thrombosis diseases.
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