(191cq) Exploiting the PAF Receptor to Target Infectious Diseases in the Lungs

Many bacterial pathogens that cross cell membranes in the lungs express lipooligosaccharides (LOS) laden with phosphorylcholine (CHoP) moieties. Our lab has demonstrated that these CHoP-containing LOS interact with the PAF receptor on lung cells. Previous students have explored using CHoP-containing LOS as targeting ligands for particles, but there is an inherent toxicity in these difficult-to-purify bacterial extracts. Currently, we are approaching this challenge by using CHoP-containing synthetic polymer coatings as a means of imbuing our particles with targeting to the PAF receptor for targeted uptake. We are investigating copolymer systems, so we need an easily-modified platform for study. Thus, we have designed our polymers with thiol end-groups to form self-assembled monolayers onto gold nanoparticles. By modifying chain length and ion content in these polymers we modify chain behavior and charge effects of these particle coatings. These are tools that we use to modify the way these particles interact with proteins and cells to enhance their ability to effectively carry drug and gene payloads to targeted areas. The development of systems that can target specific cell or tissues is a major goal in drug delivery, and biomaterials that minimally interact with proteins in the body are of additional value in a variety of medical devices.