褐藻糖胶
溶栓
材料科学
血栓
纳米颗粒
体外
生物医学工程
生物物理学
纳米技术
化学
多糖
医学
生物化学
外科
生物
内科学
心肌梗塞
作者
Maya Juenet,Rachida Aid‐Launais,Bo Li,Alice Berger,Joël Aerts,Véronique Ollivier,Antonino Nicoletti,Didier Letourneur,Cédric Chauvierre
出处
期刊:Biomaterials
[Elsevier]
日期:2018-02-01
卷期号:156: 204-216
被引量:125
标识
DOI:10.1016/j.biomaterials.2017.11.047
摘要
Injection of recombinant tissue plasminogen activator (rt-PA) is the standard drug treatment for thrombolysis. However, rt-PA shows risk of hemorrhages and limited efficiency even at high doses. Polysaccharide-poly(isobutylcyanoacrylate) nanoparticles functionalized with fucoidan and loaded with rt-PA were designed to accumulate on the thrombus. Fucoidan has a nanomolar affinity for the P-selectin expressed by activated platelets in the thrombus. Solid spherical fluorescent nanoparticles with a hydrodynamic diameter of 136 ± 4 nm were synthesized by redox radical emulsion polymerization. The clinical rt-PA formulation was successfully loaded by adsorption on aminated nanoparticles and able to be released in vitro. We validated the in vitro fibrinolytic activity and binding under flow to both recombinant P-selectin and activated platelet aggregates. The thrombolysis efficiency was demonstrated in a mouse model of venous thrombosis by monitoring the platelet density with intravital microscopy. This study supports the hypothesis that fucoidan-nanoparticles improve the rt-PA efficiency. This work establishes the proof-of-concept of fucoidan-based carriers for targeted thrombolysis.
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