Plasma and Serum Proteins Bound to Nanoceria: Insights into Pathways by which Nanoceria may Exert Its Beneficial and Deleterious Effects In Vivo.

Journal of Nanomedicine & Nanotechnology Pub Date : 2020-01-01 Epub Date: 2020-07-17
Allan D Butterfield, Binghui Wang, Peng Wu, Sarita S Hardas, Jason M Unrine, Eric A Grulke, Jian Cai, Jon B Klein, William M Pierce, Robert A Yokel, Rukhsana Sultana
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Abstract

Nanoceria (CeO2, cerium oxide nanoparticles) is proposed as a therapeutic for multiple disorders. In blood, nanoceria becomes protein-coated, changing its surface properties to yield a different presentation to cells. There is little information on the interaction of nanoceria with blood proteins. The current study is the first to report the proteomics identification of plasma and serum proteins adsorbed to nanoceria. The results identify a number of plasma and serum proteins interacting with nanoceria, proteins whose normal activities regulate numerous cell functions: antioxidant/detoxification, energy regulation, lipoproteins, signaling, complement, immune function, coagulation, iron homeostasis, proteolysis, inflammation, protein folding, protease inhibition, adhesion, protein/RNA degradation, and hormonal. The principal implications of this study are: 1) The protein corona may positively or negatively affect nanoceria cellular uptake, subsequent organ bioprocessing, and effects; and 2) Nanoceria adsorption may alter protein structure and function, including pro- and inflammatory effects. Consequently, prior to their use as therapeutic agents, better understanding of the effects of nanoceria protein coating is warranted.

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血浆和血清蛋白结合纳米微球:纳米微球在体内发挥其有益和有害作用的途径。
纳米铈(CeO2,氧化铈纳米粒子)被认为是一种治疗多种疾病的药物。在血液中,纳米细粒被蛋白质包裹,改变其表面特性,以不同的方式呈现给细胞。关于纳米粒与血液蛋白相互作用的信息很少。目前的研究首次报道了纳米子宫颈吸附的血浆和血清蛋白的蛋白质组学鉴定。结果确定了许多血浆和血清蛋白与纳米微球相互作用,这些蛋白的正常活动调节许多细胞功能:抗氧化/解毒、能量调节、脂蛋白、信号传导、补体、免疫功能、凝血、铁稳态、蛋白质水解、炎症、蛋白质折叠、蛋白酶抑制、粘附、蛋白质/RNA降解和激素。本研究的主要意义是:1)蛋白冠可能对纳米子宫颈细胞摄取、随后的器官生物加工和效应产生积极或消极的影响;2)纳米微球吸附可改变蛋白质结构和功能,包括促炎性作用。因此,在将其用作治疗剂之前,有必要更好地了解纳米子宫颈蛋白涂层的作用。
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