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超越蛋白质冠 - 脂质对纳米载体的生物反应很重要。

Beyond the protein corona - lipids matter for biological response of nanocarriers.

机构信息

Max Planck Institute for Polymer Research, Ackermannweg 10, 55128 Mainz, Germany; Dermatology Clinic, University Medical Center Mainz, Langenbeckstraße 1, 55131 Mainz, Germany.

Max Planck Institute for Polymer Research, Ackermannweg 10, 55128 Mainz, Germany.

出版信息

Acta Biomater. 2018 Apr 15;71:420-431. doi: 10.1016/j.actbio.2018.02.036. Epub 2018 Mar 7.

Abstract

UNLABELLED

The interaction of nanocarriers with blood plasma components influences the biological response, and therefore, it needs to be controlled. Whereas protein adsorption to nanocarriers has been investigated to a large extent, the role of lipid interaction for drug delivery and its biological effect is not yet clear. However, lipids represent an important constituent of blood plasma and are usually bound in the form of lipoproteins. Because already for many nanocarrier systems an enrichment of apolipoproteins in their protein corona was reported, we examine the interaction of lipoproteins with nanocarriers. If interaction occurs in terms of lipoprotein adsorption, two scenarios are possible: adsorption of intact lipoprotein complexes or disintegration of the complexes with adsorption of the single components. To investigate the interaction and clarify which scenario occurs, polymeric model nanoparticles and different lipoprotein types have been studied by isothermal titration calorimetry, transmission electron microscopy, and other methods. Our data indicate that upon contact with polymeric nanoparticles, disintegration of lipoproteins and adsorption of lipids occurs. Further, the effect of lipoprotein adsorption on cell uptake has been examined, and a major effect of the lipoproteins has been found.

STATEMENT OF SIGNIFICANCE

It is now well accepted that nanomaterials developed as diagnostic or therapeutic carrier systems need to be well characterized in terms of biological responses inside an organism. Many studies have already shown that proteins adsorb to the surface of a nanomaterial and create a new interface that define the identity of the material. However, the presence of other surface-active components of the blood plasma and how they interact with nanomaterials has been much less investigated. Thus, this study aims at providing a significant contribution to understanding the interaction mechanism between lipoproteins and nanomaterials. Since lipoproteins transport a high amount of lipids, which are surface-active molecules, the demonstrated interactions can go as far as complete lipoprotein disintegration.

摘要

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纳米载体与血浆成分的相互作用会影响生物反应,因此需要加以控制。尽管已经对纳米载体的蛋白质吸附进行了广泛的研究,但脂质相互作用对于药物传递及其生物学效应的作用尚不清楚。然而,脂质是血浆的重要组成部分,通常以脂蛋白的形式结合。由于已经有许多纳米载体系统报道了载脂蛋白在其蛋白质冠中的富集,因此我们研究了脂蛋白与纳米载体的相互作用。如果以脂蛋白吸附的形式发生相互作用,则有两种可能的情况:完整脂蛋白复合物的吸附或复合物的解体以及单个成分的吸附。为了研究相互作用并阐明发生了哪种情况,我们使用等温滴定微量热法、透射电子显微镜和其他方法研究了聚合物模型纳米粒子和不同的脂蛋白类型。我们的数据表明,与聚合物纳米粒子接触时,脂蛋白会解体并吸附脂质。此外,还研究了脂蛋白吸附对细胞摄取的影响,发现脂蛋白有很大的影响。

意义陈述

现在人们普遍接受,作为诊断或治疗载体系统开发的纳米材料需要根据其在生物体内部的生物反应进行很好的特性描述。许多研究已经表明,蛋白质会吸附在纳米材料的表面并形成一个新的界面,从而定义材料的特性。然而,血浆中其他表面活性剂成分的存在以及它们与纳米材料的相互作用却很少被研究。因此,这项研究旨在为理解脂蛋白与纳米材料之间的相互作用机制提供重要贡献。由于脂蛋白携带大量的脂质,这些脂质是表面活性剂分子,因此所证明的相互作用可以导致脂蛋白完全解体。

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