Effect of Engineered Solid and Mesoporous Silica Particles Physical Properties on In Vitro Toxicity
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Effect of Engineered Solid and Mesoporous Silica Particles Physical Properties on In Vitro Toxicity Kennedy Nguyen1, Gayatri Premasekharan1, Alexander Yuen1, Henry J. Forman2, 3, and Valerie J. Leppert1 Schools of Engineering1 and Natural Sciences2, University of California, Merced, 5200 North Lake Road, Merced, CA 95343, U.S.A. Davis School of Gerontology3, University of Southern California, Ethel Percy Andrus Gerontology Center, 3715 McClintock Avenue, Los Angeles, CA 90089-0191, U.S.A. ABSTRACT Mesoporous silica is of current interest for therapeutic applications, such as drug delivery, because of its small size and internal pore structure into which small molecules can be adsorbed. However, while the toxicity literature is extensive for micron-sized crystalline silica due to occupational health concerns, there is relatively little information available for mesoporous silica. Here, solid silica and mesoporous silica particles are characterized using SEM, DLS, XRD, and BET analysis; and their toxicities assessed using a modified MTT assay for cell viability and DPPP assay for lipid peroxidation. On a mass basis, mesoporous silica reduces cell viability from 82 + 8% to 73 + 16% compared to solid silica, likely due to the decreased density and therefore increased number of particles and particle surface area. This modest increase in toxicity, compared to the dramatic 600X increase in total surface area for mesoporous silica, from both pore and particle surfaces, suggests that the toxicity mechanism depends on the surface area available to the cell and not the total surface area. DPPP results support this conclusion and indicate that membrane lipid peroxidation is involved. INTRODUCTION Mesoporous silica is of current interest for therapeutic applications [1-3], due to its internal pore structure, which can adsorb small molecules. However, relatively little information exists on the toxicity of mesoporous silica that may arise as a result of a myriad of factors, including particle size and size distribution, shape, agglomeration, crystal structure, chemical composition, surface chemistry and charge, and porosity [4-10]. This study compares the physiochemical characteristics and toxicity of mesoporous and solid amorphous silica particles of similar size. The particles are characterized for size, size distribution, crystal structure, and surface area; and toxicity is determined by modified (3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide) (MTT) assay for cell viability and Diphenyl-1-pyrenylphosphine (DPPP) assay for lipid peroxidation. EXPERIMENTAL DETAILS Engineered solid silica (Microspheres-nanospheres) and mesoporous silica (Tianjin Chemist Scientific) particles size-separated to a 1-3 µm fraction using a technique for zeolites [11] are characterized using the Scanning Electron Microscope (SEM) for particle size and size
distribution; while Dynamic Light Scattering (DLS) is used to determine the hydrodynamic diameter of mesoporous particles in freshly prepared suspensions in water at room temperat
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