Department of Chemistry, Gachon University, Seongnam, Gyeonggi 13120, Republic of Korea.
Department of Chemistry, Wonkwang University, Iksan, Jeonbuk 54538, Republic of Korea.
Langmuir. 2021 Aug 17;37(32):9755-9763. doi: 10.1021/acs.langmuir.1c01182. Epub 2021 Aug 4.
Apolipoproteins have been often found to be highly enriched in the serum protein coronas produced on various engineered nanoparticles (NPs), which is also known to greatly influence the behaviors of protein corona NPs in the biological systems. As most of the apolipoproteins in blood are associated with lipoproteins, it suggests the active involvement of lipoproteins in the formation of biomolecular coronas on NPs. However, the interactions of lipoprotein complexes with NPs in the corona formation have been rarely understood. In this study, to obtain insights into the interactions, the formation of biomolecular coronas of high-density lipoproteins (HDLs) on the PEGylated gold NPs (PEG-AuNPs) of various sizes (20-150 nm dia.) was investigated as a model system. The results of this study revealed a noticeable size dependence, which is a drastic increase in the affinity of HDL for larger NPs and thus less-curved NP surfaces. For example, only a few HDLs per NP, which correspond to 5% surface coverage, were found to constitute the hard coronas of HDLs on 20 nm PEG-AuNPs, whereas 73% surface coverage was assessed for larger 150 nm PEG-AuNPs. However, the relative affinities of HDL and apolipoprotein A-1 (APOA1) examined in competition with human serum albumin exhibited the opposite size dependences, which suggests that the adsorption of HDLs is not driven by the constituent protein, APOA1. In fact, the total strength of non-covalent intermolecular interactions between a HDL particle and a NP relies on the physical contact between the two particles, which thus depends on the varying curvatures of spherical NPs in this case. Therefore, it was concluded that it is whole HDL complex that interacts with the spherical PEG-AuNPs in the initial stage of adsorption toward biomolecular coronas, which is unveiled by the distinct size dependence observed in this study.
载脂蛋白在各种工程纳米粒子（NPs）上产生的血清蛋白冠中含量极高，这一点已被广泛发现，并且已知这极大地影响了蛋白质冠 NPs 在生物系统中的行为。由于血液中的大多数载脂蛋白都与脂蛋白有关，这表明脂蛋白在 NPs 上形成生物分子冠的过程中起着积极的作用。然而，脂蛋白复合物与 NPs 在形成蛋白质冠过程中的相互作用却很少被理解。在这项研究中，为了深入了解这些相互作用，以聚乙二醇化金纳米粒子（PEG-AuNPs）为模型体系，研究了不同大小（20-150nm 直径）的高密度脂蛋白（HDLs）在纳米粒子上形成生物分子冠的过程。研究结果表明存在明显的尺寸依赖性，即 HDL 与较大 NPs 的亲和力显著增加，从而导致 NP 表面的曲率减小。例如，在 20nm 的 PEG-AuNPs 上，只有少数几个 HDL（对应于 5%的表面覆盖率）被发现构成 HDL 的硬冠，而对于较大的 150nm PEG-AuNPs，则评估了 73%的表面覆盖率。然而，在与人血清白蛋白竞争时，考察的 HDL 和载脂蛋白 A-1（APOA1）的相对亲和力表现出相反的尺寸依赖性，这表明 HDL 的吸附不是由组成蛋白 APOA1 驱动的。事实上，HDL 颗粒与 NP 之间的非共价分子间相互作用的总强度取决于两个颗粒之间的物理接触，这在这种情况下取决于球形 NPs 的曲率变化。因此，可以得出结论，在吸附到生物分子冠的初始阶段，是整个 HDL 复合物与球形 PEG-AuNPs 相互作用，这是由本研究中观察到的明显尺寸依赖性揭示的。
