466807 Physiochemical Properties of Nanoparticles Determine Their in Vitro Cytotoxicity
In order to elucidate the effects of particle surface characteristics, studies were conducted with PEG 2k, 5k and 20k, as well as aminated silica nanoparticles. Two nanoparticle sizes, 60 and 120 nm, were chosen to draw size effect comparisons between the particles. These particles are generally recognized as a safe material by the Food and Drug Administration and provided a uniform foundation via size distribution, surface characteristics and mild reaction chemistry that precluded any nanoparticle-mediated effects.
In vitro distribution of the silica nanoparticles was found to directly correlate with their surface coating. Pegylated particles were found to remain interspersed among the CHO cells, whereas amine coated particles were found to produce punctate regions of fluorescence on and around the cells. Confocal microscopy confirmed uptake over simple surface association of the nanoparticles. Similar trends were correlated with flow cytometry. It was found that all PEG coatings decreased particle uptake by the CHO cells in comparison to those with an amine coating. The aminated particles had the greatest effect on cell growth. The 60 nm particles yielded greater half maximal inhibitory concentrations (IC50) values over the 120 nm particles. The IC50 values for 60 nm aminated, PEG 2k, 5k and 20k particles were found to be 0.42 ± 0.18, 2.58 ± 0.09, 1.75 ± 0.11 and 3.535 ± 0.15 mg/mL, respectively. The IC50 values for the 120 nm aminated, PEG 2k, 5k and 20k particles were found to be 0.59 ± 0.05, 1.435 ± 0.13, 1.57 ± 0.125 and 1.333 ± 0.17 mg/mL. Growth inhibition directly correlated with particle concentration regardless of surface character. Pegylated 60 nm particles showed the greatest differences among their PEG coatings whereas the 120 nm pegylated particles showed similar results among all PEG sizes.
This study found that size and surface coatings have a dramatic influence on the cell viability and uptake in vitro. In addition, these studies show there may be an interplay between both of these variable sets. This work has provided a basis of comparison that could be extended to various nanoparticle systems. Understanding the impact of widely used solid nanoparticle compositions, sizes, coatings and their combinations on mammalian systems is an important step in developing robust drug delivery vehicles.
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