抗血栓纳米偶联物的开发，阻断整合素 α2β1-胶原相互作用。
Development of antithrombotic nanoconjugate blocking integrin α2β1-collagen interactions.
机构信息
Department of Biochemical Engineering and Key Laboratory of Systems Bioengineering of the Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, People's Republic of China.
School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, People's Republic of China.
出版信息
Sci Rep. 2016 May 19;6:26292. doi: 10.1038/srep26292.
An antithrombotic nanoconjugate was designed in which a designed biomimetic peptide LWWNSYY was immobilized to the surface of poly(glycidyl methacrylate) nanoparticles (PGMA NPs). Our previous work has demonstrated LWWNSYY to be an effective inhibitor of integrin α2β1-collagen interaction and subsequent thrombus formation, however its practical application suffered from the formation of clusters in physiological environment caused by its high hydrophobicity. In our present study, the obtained LWWNSYY-PGMA nanoparticles (L-PGMA NPs) conjugate, with an improved dispersibility of LWWNSYY by PGMA NPs, have shown binding to collagen receptors with a Kd of 3.45 ± 1.06 μM. L-PGMA NPs have also proven capable of inhibiting platelet adhesion in vitro with a reduced IC50 of 1.83 ± 0.29 μg/mL. High inhibition efficiency of L-PGMA NPs in thrombus formation was further confirmed in vivo with a 50% reduction of thrombus weight. Therefore, L-PGMA NPs were developed as a high-efficiency antithrombotic nanomedicine targeted for collagen exposed on diseased blood vessel wall.
设计了一种抗血栓纳米缀合物，其中固定化了设计的仿生肽 LWWNSYY 到聚（甲基丙烯酸缩水甘油酯）纳米颗粒 (PGMA NPs) 的表面。我们之前的工作已经证明 LWWNSYY 是整合素 α2β1-胶原相互作用和随后血栓形成的有效抑制剂，然而，由于其高疏水性，其在生理环境中形成聚集体，限制了其实际应用。在本研究中，获得的 LWWNSYY-PGMA 纳米颗粒（L-PGMA NPs）缀合物通过 PGMA NPs 提高了 LWWNSYY 的分散性，显示出与胶原蛋白受体的结合 Kd 为 3.45±1.06 μM。L-PGMA NPs 还被证明能够在体外抑制血小板黏附，IC50 降低至 1.83±0.29 μg/mL。体内血栓形成的高抑制效率进一步得到证实，血栓重量减少了 50%。因此，L-PGMA NPs 被开发为一种针对病变血管壁上暴露的胶原蛋白的高效抗血栓纳米药物。
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