(478d) Silica Nanoparticle Surface Characteristics Dictate in vitro Cytotoxic Behavior

Solid nanoparticles have proven useful in overcoming many of the barriers to drug delivery. Additional development has seen the attachment of a myriad of surface coatings such as polyethylene glycol (PEG). This commonly used PEG layer masks particles from innate host defence mechanisms within the body and increases circulation half-life of the therapeutic upon injection. Although this approach is widely accepted, the underlying mechanism is not well understood. This study examined the effect of hydrophilic surface coatings on solid silica nanoparticles with their interactions with Chinese Hamster Ovary (CHO) cells. Specifically, we examined the effect of differing Dalton weights of PEG on intracellular uptake and viability. Studies were conducted with amine and PEG 2k, 5k and 20k coated silica nanoparticles. Two nanoparticle sizes, 60 and 120 nm, were chosen to draw size effect comparisons.

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. Growth inhibition directly correlated with particle concentration regardless of surface character.

This study found that size and surface coatings have a dramatic influence on the CHO cell viability. Additional studies are needed to elucidate the 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, surface coatings and their combinations on mammalian systems is an important step towards developing robust drug delivery vehicles.