(611f) Limiting Protein Adsorption on Drug Carriers with Bio-Inspired, Zwitterionic Polymer Coatings

Targeted drug delivery systems show great promise in increasing the efficacy of drugs while also lowering off-target side effects. However, biofouling of the drug carrier surfaces when the carriers interact with protein-rich biological fluids such as blood and mucus limits delivery efficiency. This protein coating (or protein corona) alters carrier interactions with cells. Non-fouling surfaces can be found in nature. In particular, bacteria have developed mechanisms to overcome protein adsorption and simultaneously enhance cellular uptake by expressing zwitterionic molecules, such as phosphorylcholine, on their surfaces. The goal of this research is to adapt the mechanisms used by bacteria to combat protein adsorption, while maintaining cell uptake. We have synthesized zwitterionic phosphorylcholine-containing methacrylate polymers using reversible addition-fragmentation chain transfer (RAFT) thermal polymerization with molecular weights ranging from 5 to 30 kDa. The polymers were attached to 100 nm gold nanoparticles, resulting in a more neutral zeta potential and no change in hydrodynamic diameter. Nanoparticles were then challenged with AB human serum and bronchoalveolar lavage fluid (BALF) with protein concentrations ranging from 1-6 mg/ml. A significant decrease in protein adsorption for polymer-coated gold nanoparticles was observed compared to bare gold nanoparticle surfaces. Minimal toxicity was observed in four lung cell lines to all reagents used in the polymer synthesis, as well as nanoparticles. Thus, zwitterionic phosphocholine-laden polymers were successful at decreasing protein adsorption while not inducing toxicity in lung cells. Current studies are focused on cellular uptake in the four cell lines, and the generation of polymers with varying levels of phosphorylcholine on the polymer backbone to decrease steric hindrance between phosphocholine side chains.