Optimizing Nanoparticle Surface Characteristics to Minimize in Vitro Cytotoxicity

The study of nanoparticles is a tremendous field for discovery involving the efficient and effective delivery of therapeutics to specific target sites. Not only can modified nanoparticles minimize the affects of systemic blood circulatory delivery, but they also induce longer lifetimes of the therapeutic once delivered in vivo. Silica nanoparticles (SNPs) have been chosen for this project due to inherent biocompatibility, thermal stability, low toxicity and high range of functionalization. Specifically for drug delivery, the target size of these nanoparticles is between 50nm to 100nm. Through the use of the Stöber method, the target range of particles has been produced by adjusting the concentrations of various reagents within the reaction. Since surface characteristics have proven in literature to significantly affect performance of these nanoparticles within the human body, polymer coatings, such as poly(ethylene glycol) (PEG), have been examined as coatings to improve the half-life upon injection of the therapeutic. Although this approach is highly utilized within present research, the mechanism is not well understood, and there is even less knowledge concerning which PEG lengths are appropriate and optimal. Through this research, progress will be made in determining the optimal PEG length appropriate for SNPs to efficaciously minimize in vitro cytotoxicity, leading to future applications within the human body. Cellular uptake and viability studies are being conducted with particles covered in various lengths of PEG. These experiments are expected to produce a standard comparison on the effects of differently sized PEG. Within these experiments, Chinese Hamster Ovary cells are used due to their widespread use in cytotoxicity and uptake studies throughout literature. Comparisons between particles taken up by cells and those simply associated with cell surfaces will be made using confocal microscopy and flow cytometry. In order to efficaciously determine effects PEG length may have on particle uptake and/or toxicity, significant characterization will be conducted, including silica and PEG concentration determination.