Bian Yingxin, Song Danhong, Fu Zejun, Jiang Chao, Xu Chen, Zhang Lei, Wang Kun, Wang Shujun, Sun Dongping
Institute of Chemicobiology and Functional Materials, School of Chemistry and Chemical Engineering, Nanjing University of Science and Technology, 200 Xiao Ling Wei, Nanjing 210094, China.
Department of Physiology and Pathophysiology, Shanghai Key Laboratory of Bioactive Small Molecules, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
J Colloid Interface Sci. 2023 May 15;638:672-685. doi: 10.1016/j.jcis.2023.01.129. Epub 2023 Feb 7.
Known to be biocompatible and hemocompatible, polyethylene glycol (PEG) has been widely used as anti-fouling coating of biomaterials. Nanoparticles coated with functionalized PEG were also investigated for their nano-cell interactions, but seldomly on the coagulation system, especially with platelets. Both experiments and molecular dynamic simulations indicate that terminal carboxylation of PEG promotes its binding with calcium, especially in the ionized form, which makes it potential anticoagulants. Further, the carboxyl PEGylated magnetic nanoparticle (HOOC-PEG-MNP) exhibits significantly increased anticoagulant and antiplatelet properties, by entering the open canalicular system (OCS) of human platelets and binding with the cytoplasmic calcium ions. HOOC-PEG-MNP also acts as effective thrombolytic agents in dissolving mature blood clots under oscillating magnetic field both in vitro and in vivo. Therefore, the carboxyl PEGylated magnetic nanoparticles are prototype agents for antithrombotic and thrombolytic therapies and provide a versatile platform for targeted and effective treatments of acute cardiovascular diseases.
聚乙二醇（PEG）具有生物相容性和血液相容性，已被广泛用作生物材料的抗污涂层。人们也研究了功能化PEG包覆的纳米颗粒与纳米细胞的相互作用，但很少涉及凝血系统，尤其是与血小板的相互作用。实验和分子动力学模拟均表明，PEG的末端羧基化促进了其与钙的结合，尤其是离子化形式的钙，这使其具有潜在的抗凝血作用。此外，羧基聚乙二醇化磁性纳米颗粒（HOOC-PEG-MNP）通过进入人血小板的开放小管系统（OCS）并与细胞质钙离子结合，表现出显著增强的抗凝血和抗血小板特性。HOOC-PEG-MNP在体外和体内的振荡磁场下溶解成熟血凝块时也作为有效的溶栓剂。因此，羧基聚乙二醇化磁性纳米颗粒是抗血栓形成和溶栓治疗的原型药物，并为急性心血管疾病的靶向和有效治疗提供了一个多功能平台。
