Analysis of SiO₂ nanoparticles binding proteins in rat blood and brain homogenate

Kyu Hwan Shim,¹ John Hulme,¹ Eun Ho Maeng,² Meyoung-Kon Kim,³ Seong Soo A An<sup>1

1</sup>Department of Bionano Technology, Gachon Medical Research Institute, Gachon University, Sungnam-si, ²Department of Analysis, KTR, Kimpo, Gyeonggi-do, ³Department of Biochemistry and Molecular Biology, Korea University Medical School and College, Seoul, South Korea


Abstract: A multitude of nanoparticles, such as titanium oxide (TiO₂), zinc oxide, aluminum oxide, gold oxide, silver oxide, iron oxide, and silica oxide, are found in many chemical, cosmetic, pharmaceutical, and electronic products. Recently, SiO₂ nanoparticles were shown to have an inert toxicity profile and no association with an irreversible toxicological change in animal models. Hence, exposure to SiO₂ nanoparticles is on the increase. SiO₂ nanoparticles are routinely used in numerous materials, from strengthening filler for concrete and other construction composites, to nontoxic platforms for biomedical application, such as drug delivery and theragnostics. On the other hand, recent in vitro experiments indicated that SiO₂ nanoparticles were cytotoxic. Therefore, we investigated these nanoparticles to identify potentially toxic pathways by analyzing the adsorbed protein corona on the surface of SiO₂ nanoparticles in the blood and brain of the rat. Four types of SiO₂ nanoparticles were chosen for investigation, and the protein corona of each type was analyzed using liquid chromatography-tandem mass spectrometry technology. In total, 115 and 48 plasma proteins from the rat were identified as being bound to negatively charged 20 nm and 100 nm SiO₂ nanoparticles, respectively, and 50 and 36 proteins were found for 20 nm and 100 nm arginine-coated SiO₂ nanoparticles, respectively. Higher numbers of proteins were adsorbed onto the 20 nm sized SiO₂ nanoparticles than onto the 100 nm sized nanoparticles regardless of charge. When proteins were compared between the two charges, higher numbers of proteins were found for arginine-coated positively charged SiO₂ nanoparticles than for the negatively charged nanoparticles. The proteins identified as bound in the corona from SiO₂ nanoparticles were further analyzed with ClueGO, a Cytoscape plugin used in protein ontology and for identifying biological interaction pathways. Proteins bound on the surface of nanoparticles may affect functional and conformational properties and distributions in complicated biological processes.

Keywords: silica, nanoparticles, protein corona, plasma, brain homogenate, nanotoxicity

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