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首页> 外文期刊>Acta biomaterialia >Controllable inhibition of cellular uptake of oxidized low-density lipoprotein: structure-function relationships for nanoscale amphiphilic polymers.
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Controllable inhibition of cellular uptake of oxidized low-density lipoprotein: structure-function relationships for nanoscale amphiphilic polymers.

机译：氧化低密度脂蛋白对细胞摄取的可控抑制：纳米级两亲聚合物的结构-功能关系。

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摘要

A family of anionic nanoscale polymers based on amphiphilic macromolecules (AMs) was developed for controlled inhibition of highly oxidized low-density lipoprotein (hoxLDL) uptake by inflammatory macrophage cells, a process that triggers the escalation of a chronic arterial disease called atherosclerosis. The basic AM structure is composed of a hydrophobic portion formed from a mucic acid sugar backbone modified at the four hydroxyls with lauroyl groups conjugated to hydrophilic poly(ethylene glycol) (PEG). The AM structure-activity relationships were probed by synthesizing AMs with six key variables: length of the PEG chain, carboxylic acid location, type of anionic charge, number of anionic charges, rotational motion of the anionic group, and PEG architecture. All AM structures were confirmed by nuclear magnetic resonance spectroscopy and their ability to inhibit hoxLDL uptake in THP-1 human macrophage cells was compared in the absence and presence of serum. We report that AMs with one, rotationally restricted carboxylic acid within the hydrophobic portion of the polymer was sufficient to yield the most effective AM for inhibiting hoxLDL internalization by THP-1 human macrophage cells under serum-containing conditions. Further, increasing the number of charges and altering the PEG architecture in an effort to increase serum stabilization did not significantly impair the ability of AMs to inhibit hoxLDL internalization, suggesting that selected modifications to the AMs could potentially promote multifunctional characteristics of these nanoscale macromolecules.
机译：开发了一种基于两亲大分子（AMs）的阴离子纳米级聚合物家族，用于控制性抑制炎性巨噬细胞摄取高氧化低密度脂蛋白（hoxLDL），这一过程触发了称为动脉粥样硬化的慢性动脉疾病的升级。 AM的基本结构由疏水性部分组成，该疏水性部分由在四个羟基上修饰的具有月桂酰基团的粘糖基糖骨架形成，该月桂酰基团与亲水性聚乙二醇（PEG）共轭。通过合成具有六个关键变量的AM来探讨AM结构与活性的关系：PEG链的长度，羧酸的位置，阴离子电荷的类型，阴离子电荷的数量，阴离子基团的旋转运动和PEG结构。通过核磁共振波谱确认了所有AM结构，并在无血清和有血清的情况下比较了它们抑制THP-1人巨噬细胞摄取hoxLDL的能力。我们报道在聚合物的疏水部分内具有一种旋转受限的羧酸的AMs足以产生最有效的AM，以抑制THP-1人巨噬细胞在含血清条件下抑制hoxLDL内在化。此外，增加电荷数量和改变PEG结构以增加血清稳定性并没有显着削弱AM抑制hoxLDL内在化的能力，这表明对AM的选择修饰可能会促进这些纳米级大分子的多功能特性。

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