Nanoparticles (NPs) that are exposed to blood are coated with an assortment of proteins that establish their biological identity by forming the interface between the NP and the cells and tissues of the body. The biological relevance of this protein corona is often overlooked during toxicological assessments of NPs. However, accurate interpretation of biological outcomes following exposure to NPs, including activation of coagulation, opsonization of pathogens, and cellular phagocytosis, must take this adsorbed proteome into account. In this study, we examined protein coronas on the surface of five poly(acrylic acid) (PAA) metal-oxide NPs (TiO₂, CeO₂, Fe₂O₃, ZnO, and PAA-capsules) following exposure to human plasma for key markers of various host response pathways, including humoral immunity and coagulation. We also evaluated the impacts of pre-exposing serum proteins to PAA-NPs on the opsonization and phagocytosis of bacteria by two immune cell lines. Results demonstrated that each PAA-NP type adsorbed a unique profile of blood proteins and that protein-coated PAA-NPs significantly inhibited human plasma coagulation with PAA-zinc oxide NPs and their associated proteome fully abrogating clotting. Protein-coated PAA-NPs also resulted in a 50% increase in phagocytic activity of RBL-2H3 cells and a 12.5% increase in phagocytic activity in the RAW 264.7 cell line. We also identified numerous structural, coagulation, and immune-activating proteins in the adsorbed protein corona, which resulted in altered biological function. Overall, our findings demonstrate that the formation of protein coronas on the surface of NPs plays an important role in directing the biological outcomes of opsonization, cell phagocytosis, and blood coagulation.

中文翻译：

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聚合物包覆的纳米颗粒蛋白质电晕形成增强先天免疫细胞对细菌的吞噬作用并抑制人血浆中的凝固。

暴露在血液中的纳米颗粒 (NP) 涂有各种蛋白质，这些蛋白质通过在 NP 与身体细胞和组织之间形成界面来建立其生物学特性。在 NP 的毒理学评估期间，这种蛋白质电晕的生物学相关性经常被忽视。然而，对暴露于 NPs 后的生物学结果的准确解释，包括凝血的激活、病原体的调理作用和细胞吞噬作用，必须考虑到这种吸附的蛋白质组。在这项研究中，我们检查了五种聚（丙烯酸）（PAA）金属氧化物纳米颗粒（TiO ₂、CeO ₂、Fe ₂ O ₃、ZnO 和 PAA 胶囊）暴露于人血浆后，作为各种宿主反应途径的关键标志物，包括体液免疫和凝血。我们还评估了将血清蛋白预暴露于 PAA-NPs 对两种免疫细胞系对细菌的调理作用和吞噬作用的影响。结果表明，每种 PAA-NP 类型都吸附了独特的血液蛋白质谱，并且蛋白质包覆的 PAA-NP 显着抑制了 PAA-氧化锌 NP 及其相关蛋白质组完全消除凝血的人血浆凝固。蛋白质包被的 PAA-NP 还导致 RBL-2H3 细胞的吞噬活性增加 50%，RAW 264.7 细胞系的吞噬活性增加 12.5%。我们还在吸附的蛋白冠中鉴定了许多结构、凝血和免疫激活蛋白，从而导致生物功能改变。总体而言，我们的研究结果表明，NPs 表面蛋白冠的形成在指导调理作用、细胞吞噬作用和血液凝固的生物学结果方面起着重要作用。