Nanoscale anionic macromolecules for selective retention of low-density lipoproteins
Nanoscale anionic macromolecules for selective retention of low-density lipoproteins
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DOI：
10.1016/j.biomaterials.2004.09.038
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发表时间：
2005-06-01
期刊：
影响因子：
14
通讯作者：
Moghe, PV
中科院分区：
文献类型：
--
作者：
Chnari, E;Lari, HB;Moghe, PV
合成设计的模拟糖胺聚糖电荷特性的阴离子纳米载体在动脉粥样硬化治疗过程中可能会螯合低密度脂蛋白（LDL）。在这项研究中，我们探讨了15-20 nm的阴离子胶束形成的两亲性蝎状大分子（ASCM）作为积木的LDL保留。大分子包含四个连接到粘酸和线性聚乙二醇（PEG）片段的脂肪族链，以形成具有疏水核和亲水冠的胶束纳米载体。动态光散射和透射电子显微镜研究表明，羧基封端的纳米载体（20 nm）螯合LDL（22 nm），产生直径为60-90 nm的复合物，但中性乙氧基封端的纳米载体不保留LDL。此外，羧基封端的纳米载体始终与未氧化的LDL（相对电泳迁移率，REM = 1.0）和轻度氧化的LDL（REM = 1.5）结合，但不与高度氧化的LDL（REM = 3.6）结合，而中性纳米载体根本没有显示出偏好/亲和力，表明纳米载体-LDL结合是电荷依赖性的。未氧化的低密度脂蛋白的结合亲和力差异充电的纳米载体，形成不同比例的羧酸酯和乙氧基封端的大分子，进行了定量。100%羧化纳米载体引起最高的结合亲和力（Kd = 567 nm），而混合胶束引起显着较低水平的结合亲和力。我们的研究结果突出了合成设计的纳米材料在脂蛋白保留方面的前景，这是管理动脉粥样硬化升级的关键步骤。(C)2004爱思唯尔有限公司保留所有权利。
Synthetically designed anionic nanocarriers that mimic the charge properties of glycosaminoglycans can potentially sequester low-density lipoproteins (LDL) during the treatment of atherosclerosis. In this study, we explore the LDL retentivity of 15-20 nm anionic micelles formed from amphiphilic scorpion-like macromolecules (AScMs) as building blocks. The macromolecules comprise four aliphatic chains attached to mucic acid and a linear polyethylene glycol (PEG) segment to form micellar nanocarriers with a hydrophobic core and hydrophilic corona. Dynamic light scattering and transmission electron microscopy studies indicate that the carboxylate-terminated nanocarriers (20 nm) sequester LDL (22 nm), resulting in complexes with a diameter of 60-90 nm, but neutral ethoxy-terminated nanocarriers do not retain LDL. Further, carboxylate-terminated nanocarriers consistently bound to unoxidized LDL (Relative Electrophoretic Mobility, REM = 1.0) and mildly oxidized LDL (REM = 1.5), but not highly oxidized LDL (REM = 3.6), whereas the neutral nanocarriers displayed no preference/affinity at all, indicating that the nanocarrier-LDL binding is charge-dependent. The binding affinity of unoxidized LDL for differentially charged nanocarriers, formed from varying ratios of carboxylate- and ethoxy-terminated macromolecules, was quantified. The 100% carboxylated nanocarriers elicited the highest binding affinity (K-d = 567 nm), whereas mixed micelles elicited significantly lower levels of binding affinity. Our results highlight the promise of synthetically designed nanomaterials in lipoprotein retention, a key step in managing the escalation of atherosclerosis. (C) 2004 Elsevier Ltd. All rights reserved.