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人工高密度脂蛋白纳米颗粒在心血管研究中的应用。

Artificial High Density Lipoprotein Nanoparticles in Cardiovascular Research.

机构信息

Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Biophysics, Medical University of Graz, Neue Stiftingtalstraße 6/IV, 8010 Graz, Austria.

出版信息

Molecules. 2019 Aug 2;24(15):2829. doi: 10.3390/molecules24152829.

Abstract

Lipoproteins are endogenous nanoparticles which are the major transporter of fats and cholesterol in the human body. They play a key role in the regulatory mechanisms of cardiovascular events. Lipoproteins can be modified and manipulated to act as drug delivery systems or nanocarriers for contrast agents. In particular, high density lipoproteins (HDL), which are the smallest class of lipoproteins, can be synthetically engineered either as nascent HDL nanodiscs or spherical HDL nanoparticles. Reconstituted HDL (rHDL) particles are formed by self-assembly of various lipids and apolipoprotein AI (apo-AI). A variety of substances including drugs, nucleic acids, signal emitting molecules, or dyes can be loaded, making them efficient nanocarriers for therapeutic applications or medical diagnostics. This review provides an overview about synthesis techniques, physicochemical properties of rHDL nanoparticles, and structural determinants for rHDL function. We discuss recent developments utilizing either apo-AI or apo-AI mimetic peptides for the design of pharmaceutical rHDL formulations. Advantages, limitations, challenges, and prospects for clinical translation are evaluated with a special focus on promising strategies for the treatment and diagnosis of atherosclerosis and cardiovascular diseases.

摘要

脂蛋白是内源性纳米颗粒,是人体内脂肪和胆固醇的主要运输载体。它们在心血管事件的调节机制中起着关键作用。脂蛋白可以被修饰和操纵,以作为药物传递系统或用于对比剂的纳米载体。特别是高密度脂蛋白(HDL),是脂蛋白中最小的一类,可以被合成工程化为新生 HDL 纳米盘或球形 HDL 纳米颗粒。重组高密度脂蛋白(rHDL)颗粒是由各种脂质和载脂蛋白 AI(apo-AI)自组装形成的。多种物质包括药物、核酸、信号发射分子或染料可以被加载,使其成为治疗应用或医学诊断的有效纳米载体。本综述概述了 rHDL 纳米颗粒的合成技术、物理化学性质和 rHDL 功能的结构决定因素。我们讨论了利用 apo-AI 或 apo-AI 模拟肽设计药物 rHDL 制剂的最新进展。评估了优势、局限性、挑战和临床转化的前景,特别关注动脉粥样硬化和心血管疾病治疗和诊断的有前途的策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1ed/6695986/1165c8b3a2fa/molecules-24-02829-g001.jpg

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