(584b) Amorphous Silicon Dioxide Nanoparticle Interactions with Pulmonary Epithelial Cells with and without a Pre-Existing Protein Corona

Silicon dioxide nanoparticles are increasingly abundant in consumer products and industrial applications, which increases their potential exposure to humans. In addition, these nanoparticles are under investigation for biomedical applications within the body such as targeted drug delivery. In either case, upon entering the body, nanoparticles interact with biological fluids and are immediately coated with proteins. Ultimately, it is this protein layer that interacts with the bodyâ??s cells and tissues, and thus dictates the subsequent fate of the nanoparticles in the body. In this work, we investigated the adsorption of an abundant protein in biological fluids, albumin, to silicon dioxide nanoparticle surfaces and the impact of this protein layer on subsequent nanoparticle uptake within human cell cultures.

A previous mechanistic study conducted in our group has indicated that pH plays a strong role in the protein affinity for the nanoparticle surface (publication in preparation). Using attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy, we obtained a real-time adsorption profile for BSA on the nanoparticle surface. Protein coverage on the nanoparticle surface was quantified using thermogravimetric analysis. Results from these studies indicated that at the isoelectric point of the BSA-silicon dioxide nanoparticle complex, pH 3.7, protein coverage was highest. Whereas at physiological pH, pH 7.4, much lower adsorption was observed over the same time period.

Cellular responses to uncoated particles and particles coated at these two pHs, to model a low-coating and a high-coating of protein on the nanoparticle surface, were conducted .Two pulmonary epithelial cell lines, 16HBE14o- and A549, were chosen for these studies as models of the different regions of the lung (bronchioles and alveoli) where nanoparticles deposit. Cell viability was measured via the MTT assay, particle uptake through TEM, and inflammatory markers through ELISA. Results from these studies indicated that coated particles behaved differently than uncoated particles in every parameter examined and that uptake depended on the cell system studied.

Overall, exposure to amorphous silicon dioxide nanoparticles induced a cellular response in pulmonary epithelial cells. Since these particles impacted the two cell lines differently, the deposition location of particle in the lungs after inhalation is important for understanding their toxicity. Surface functionalization prior to cellular exposure also played a key role in the cellular response, further supporting the idea that the protein corona affects cellular recognition and responses.