Kobos Lisa M, Alqatani Saeed, Ferreira Christina R, Aryal Uma K, Hedrick Victoria, Sobreira Tiago J P, Shannahan Jonathan H
School of Health Sciences, College of Health and Human Sciences, Purdue University, West Lafayette, Indiana.
National Center for Pharmaceuticals, Life Science and Environment Research Institute, King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia.
Appl In Vitro Toxicol. 2019 Sep 1;5(3):150-166. doi: 10.1089/aivt.2019.0005. Epub 2019 Sep 17.
When nanoparticles (NPs) enter a physiological environment, a coating of biomolecules or biocorona (BC) forms on the surface. Formation of the NP-BC is dependent on NP properties, the physiological environment, and time. The BC influences NP properties and biological interactions such as cellular internalization, immune responses, biodistribution, and others, leading to pharmacological and toxicological consequences. To date, examination of the NP-BC has focused primarily on protein components and healthy conditions. Therefore, we evaluated the protein and lipid content of BCs that formed on physicochemically distinct gold nanoparticles (AuNPs) under healthy and obese conditions. A comprehensive understanding of the NP-BC is necessary for the translation of toxicity assessments to clinical applications. AuNPs with two coatings (poly-N-vinylpyrrolidone [PVP] or citrate) and diameters (20 or 100 nm) were incubated in pooled human serum, and an integrated proteomic/lipidomic approach was used to evaluate BC composition. Macrophages were utilized to evaluate differential immune responses due to variations in the AuNP-BC. AuNPs form distinct BCs based on physicochemical properties and the surrounding environment, with the obese BC containing more proteins and fewer lipids than the healthy BC. Differential macrophage inflammatory responses were observed based on AuNP properties and BC composition. Overall, these findings demonstrate that AuNP size and coating, as well as physiological environment, influence the protein and lipid composition of the BC, which impacts cellular responses following exposure. These findings demonstrate that incorporation of BCs representing distinct physiological conditions may enhance the translatability of nanosafety studies.
当纳米颗粒（NPs）进入生理环境时，其表面会形成一层生物分子或生物冠（BC）。NP-BC的形成取决于NP的性质、生理环境和时间。BC会影响NP的性质以及细胞内化、免疫反应、生物分布等生物相互作用，从而导致药理学和毒理学后果。迄今为止，对NP-BC的研究主要集中在蛋白质成分和健康状况方面。因此，我们评估了在健康和肥胖条件下，在物理化学性质不同的金纳米颗粒（AuNPs）上形成的BC的蛋白质和脂质含量。全面了解NP-BC对于将毒性评估转化为临床应用是必要的。将具有两种涂层（聚N-乙烯基吡咯烷酮[PVP]或柠檬酸盐）和两种直径（20或100nm）的AuNPs与人混合血清一起孵育，并采用综合蛋白质组学/脂质组学方法评估BC的组成。利用巨噬细胞评估由于AuNP-BC的差异而产生的不同免疫反应。AuNPs根据其物理化学性质和周围环境形成不同的BC，肥胖状态下形成的BC比健康状态下形成的BC含有更多蛋白质和更少脂质。基于AuNP的性质和BC的组成，观察到了巨噬细胞不同的炎症反应。总体而言，这些发现表明AuNP的大小和涂层以及生理环境会影响BC的蛋白质和脂质组成，进而影响暴露后的细胞反应。这些发现表明，纳入代表不同生理条件的BC可能会提高纳米安全性研究的可转化性。
