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仿生双功能磷脂-poly(acrylic acid)刷接枝多孔聚(vinyl alcohol)珠用于选择性吸附低密度脂蛋白。

Bio-inspired dual-functional phospholipid-poly(acrylic acid) brushes grafted porous poly(vinyl alcohol) beads for selective adsorption of low-density lipoprotein.

机构信息

Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Science, Nankai University, Tianjin, 300071, China.

出版信息

J Mater Chem B. 2021 Aug 28;9(32):6364-6376. doi: 10.1039/d1tb01220g. Epub 2021 Jul 23.

DOI:10.1039/d1tb01220g
PMID:34296735
Abstract

Elevated levels of low-density lipoproteins (LDL) are recognized as a crucial indicator of hyperlipidemia (HLP) and lowering of LDL levels represents an effective clinical treatment strategy. Inspired by the conjugation of phospholipid monolayers and the lipid content of the LDL particle, the current study describes the preparation of an innovative hemoperfusion adsorbent. The adsorbent was prepared by attachment of phosphatidyl ethanolamine to poly(acrylic acid) modified poly(vinyl alcohol-co-triallyl isocyanurate) beads (PVA@PAA-PE). The interaction between LDL and adsorbent mimics the lipoprotein microemulsion present in the blood and thus promotes efficient binding with high affinity. In vitro adsorption using serum from patients with HLP revealed that the LDL adsorption of PVA@PAA-PE was 4.44 times higher than that of controls and the removal rate of LDL using PVA@PAA-PE was about twice as high as that of the anti-atherogenic high-density lipoprotein (HDL). In vivo whole blood perfusion demonstrated the superior affinity of PVA@PAA-PE for LDL since LDL concentration was significantly reduced from 10.71 ± 2.36 mmol L to 6.21 ± 1.45 mmol L, while the HDL level was not severely reduced (from 0.98 ± 0.12 mmol L to 0.56 ± 0.15 mmol L). Additionally, PVA@PAA-PE exhibited excellent hemocompatibility and low cytotoxicity. Therefore, PVA@PAA-PE is a potential adsorbent for whole blood perfusion to treat hyperlipidemia.

摘要

低密度脂蛋白(LDL)水平升高被认为是高脂血症(HLP)的一个关键指标,降低 LDL 水平是一种有效的临床治疗策略。受 LDL 颗粒中磷脂单层和脂质含量的共轭启发,本研究描述了一种新型血液灌流吸附剂的制备。该吸附剂是通过将磷脂酰乙醇胺连接到聚(丙烯酸)修饰的聚(乙烯醇-co-三烯丙基异氰脲酸酯)珠(PVA@PAA-PE)上制备的。LDL 与吸附剂的相互作用模拟了血液中存在的脂蛋白微乳液,从而促进了高效结合和高亲和力。使用 HLP 患者的血清进行体外吸附表明,PVA@PAA-PE 对 LDL 的吸附能力是对照的 4.44 倍,使用 PVA@PAA-PE 去除 LDL 的速率约为抗动脉粥样硬化高密度脂蛋白(HDL)的两倍。体内全血灌注实验表明,PVA@PAA-PE 对 LDL 具有优异的亲和力,因为 LDL 浓度从 10.71±2.36mmol/L 显著降低至 6.21±1.45mmol/L,而 HDL 水平没有严重降低(从 0.98±0.12mmol/L 降低至 0.56±0.15mmol/L)。此外,PVA@PAA-PE 表现出良好的血液相容性和低细胞毒性。因此,PVA@PAA-PE 是一种用于全血灌注治疗高脂血症的潜在吸附剂。

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