Department of Molecular Medicine, Sapienza University of Rome, Viale Regina Elena 291, 00161 Rome, Italy.
Nanoscale. 2017 Nov 16;9(44):17254-17262. doi: 10.1039/c7nr06437c.
Following exposure to biological milieus (e.g. after systemic administration), nanoparticles (NPs) get covered by an outer biomolecular corona (BC) that defines many of their biological outcomes, such as the elicited immune response, biodistribution, and targeting abilities. In spite of this, the role of BC in regulating the cellular uptake and the subcellular trafficking properties of NPs has remained elusive. Here, we tackle this issue by employing multicomponent (MC) lipid NPs, human plasma (HP) and HeLa cells as models for nanoformulations, biological fluids, and target cells, respectively. By conducting confocal fluorescence microscopy experiments and image correlation analyses, we quantitatively demonstrate that the BC promotes a neat switch of the cell entry mechanism and subsequent intracellular trafficking, from macropinocytosis to clathrin-dependent endocytosis. Nano-liquid chromatography tandem mass spectrometry identifies apolipoproteins as the most abundant components of the BC tested here. Interestingly, this class of proteins target the LDL receptors, which are overexpressed in clathrin-enriched membrane domains. Our results highlight the crucial role of BC as an intrinsic trigger of specific NP-cell interactions and biological responses and set the basis for a rational exploitation of the BC for targeted delivery.
在暴露于生物环境（例如全身给药后）后，纳米颗粒（NPs）会被外层生物分子冠（BC）覆盖，这决定了它们的许多生物学结果，例如引发的免疫反应、生物分布和靶向能力。尽管如此，BC 在调节 NPs 的细胞摄取和亚细胞转运特性方面的作用仍然难以捉摸。在这里，我们采用多组分（MC）脂质 NPs、人血浆（HP）和 HeLa 细胞分别作为纳米制剂、生物流体和靶细胞的模型来解决这个问题。通过进行共聚焦荧光显微镜实验和图像相关分析，我们定量证明了 BC 促进了细胞进入机制和随后的细胞内转运的明显转变，从巨胞饮作用到网格蛋白依赖性内吞作用。纳米液相色谱串联质谱鉴定出载脂蛋白是我们在此测试的 BC 中最丰富的成分。有趣的是，这类蛋白质的靶标是 LDL 受体，它在富含网格蛋白的膜域中过表达。我们的研究结果强调了 BC 作为一种内在触发特定 NP-细胞相互作用和生物学反应的关键作用，并为基于 BC 进行靶向递药提供了基础。
