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Protein Adsorption From Biofluids on Silica Nanoparticles: Corona Analysis as a Function of Particle Diameter and Porosity.

ABSTRACT: A study on the adsorption of proteins from fetal bovine serum (FBS) on spherical dense and mesoporous silica nanoparticles with a wide range of diameters, from 70 to 900 nm, is presented. Monodisperse populations of particles with a range of diameters were obtained through modifications of the Stöber method. Extensive characterization of the particles was then performed using N2 physisorption, TEM, DLS, and ?-potential. Following serum exposure, proteomic evaluation in concert with thermogravimetric analysis revealed the associated concentrations of each protein identified in the hard corona. Small particles adsorbed the largest amount of protein, due to their larger external surface area. Proteins with low molecular weights (<50 kDa) constituted the majority of the protein corona, totaling between 60 and 80% of the total mass of adsorbed protein. Here, the higher surface curvature of small particles favors the enrichment of smaller proteins. Porosity does not promote protein adsorption but improves deposition of the low molecular weight protein fraction due to the size-exclusion effect related to pore diameter. These results have important implications for the use of dense and porous silica nanoparticles in biomedical applications.

SUBMITTER: Clemments AM

PROVIDER: S-EPMC5084906 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Protein Adsorption From Biofluids on Silica Nanoparticles: Corona Analysis as a Function of Particle Diameter and Porosity.

Clemments Alden M AM Botella Pablo P Landry Christopher C CC

ACS applied materials & interfaces 20150924 39

A study on the adsorption of proteins from fetal bovine serum (FBS) on spherical dense and mesoporous silica nanoparticles with a wide range of diameters, from 70 to 900 nm, is presented. Monodisperse populations of particles with a range of diameters were obtained through modifications of the Stöber method. Extensive characterization of the particles was then performed using N2 physisorption, TEM, DLS, and ζ-potential. Following serum exposure, proteomic evaluation in concert with thermogravime ...[more]

PMID: 26371804

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Project description:Despite increasing reports of using silica nanoparticles (SNPs) for controlled drug delivery applications, their long-term toxicity profile following intravenous administration remains unexplored. Herein, we investigated the acute (10-day) and subchronic (60-day and 180-day) toxicity of nonporous SNPs of approximately 50 nm (Stöber SNPs50) and approximately 500 nm in diameter (Stöber SNPs500), and mesoporous SNPs of approximately 500 nm in diameter (MSNPs500) upon single-dose intravenous injection into male and female immune-competent inbred BALB/c mice. The Maximum Tolerated Dose (MTD) of the particles was determined 10 days post-injection. The MTD of SNPs was administered and toxicity evaluated over 60 and 180 days. Results demonstrate that Stöber SNPs50 exhibit systemic toxicity with MTD of 103 ± 11 mg.kg-1 for female and 100 ± 6 mg.kg-1 for male mice, respectively. Toxicity was alleviated by increasing the size of the particles (Stöber SNPs500). MTD values of 303 ± 4 mg.kg-1 for female and 300 ± 13 mg.kg-1 for male were observed for Stöber SNPs500. Mesoporous SNPs500 showed considerable systemic sex-related toxicity, with MTDs ranging from 40 ± 2 mg.kg-1 to 95 ± 2 mg.kg-1 for male and female mice, respectively. Studies of SNPs showed blood toxicity as a function of physiochemical properties such as significant differences in the mean corpuscular hemoglobin (MCHC) and platelet number at day 10 and white blood cell count at day 60. Histological examination also showed size-, porosity- and time-dependent tissue toxicity. Stöber SNPs500 caused major toxic effects such as lung thrombosis, cardiac wall fibrosis and calcifications, brain infarctions with necrotizing inflammatory response, infiltrate, retinal injuries with calcification and focal gliosis, renal parenchymal damage and liver lobular inflammation dependent on the dose and time of exposure. However, tissue toxicity and accumulation of SNPs in liver observed at day 10 was greater than at day 60 and much greater than at day 180. In contrast, a dramatic increase in cytokine levels was observed at day 60. Despite the relatively high doses, SNPs did not cause subchronic toxicity at day 180 after single-dose intravenous injection. However, they showed distinct differences in the 60 day in vivo subchronic toxicity and inflammation profile as a function of surface area and size.

Dataset Information

Protein Adsorption From Biofluids on Silica Nanoparticles: Corona Analysis as a Function of Particle Diameter and Porosity.

Publications

Protein Adsorption From Biofluids on Silica Nanoparticles: Corona Analysis as a Function of Particle Diameter and Porosity.

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