To effectively treat disease, drug molecules must accumulate in sufficient amounts at a specific site in the body. To achieve this, tiny vehicles called carriers are often needed, but unwanted interactions within the body often limit their effectiveness. This project uses knowledge of the molecular interactions between bacterial/viral pathogens and human cells during human infection to design bioinspired polymer coatings for drug carriers. The project will provide deeper insight into chemical structures that simultaneously limit biofouling on the carrier surface and enhance attachment of carriers to human cells. Longer term, these results will enable the development of nanocarriers that can provide better treatment of disease by decreasing the amount of drug required for treatment and limiting side effects. This project will have a direct impact on the educational experience of students at various levels. Two graduate students will perform research for their Ph.D. theses and several undergraduate students from underrepresented groups will participate in the research. Further, a K-12 outreach program in engineering and science will utilize concepts from the research during camps throughout the state of Iowa and provide graduate and undergraduate students with opportunities for teacher training. Research results and discoveries will be disseminated through publications in peer-reviewed journals and presentations at local, national, and international conferences.
Current drug delivery strategies to target specific cells within the body are plagued by low levels of drug accumulation in the areas they are most needed. When drug carriers enter the body and interact with biological fluids, biofouling of the carrier surface occurs and new surface properties develop that control the carrier’s subsequent bio-interactions and fate. Our lack of knowledge of how to design drug carriers with appropriate properties to trigger and mediate their interactions within complex biological environments has significantly hindered progress towards efficient drug delivery. The goal of this proposal is to design a surface coating for nanocarriers to simultaneously address issues of biofouling and cell uptake in complex biological environments. Bioinspired polymeric ligands containing molecular structures that mimic the surfaces of respiratory pathogens known to efficiently penetrate human fluids and the lung epithelium will be developed. The ability of ligand-coated nanoparticle to target lung epithelial cells submerged in natural secretions will be experimentally observed and quantified. Two independent techniques will be pursued to evaluate the molecular recognition of the ligands. First, a high-throughput, optical biosensor technique will quantify the real-time cellular responses to receptor-ligand interactions in living cells. Second, a 3-D homology modeling approach will elucidate the ability of the ligands to dock into the receptor binding pocket. Results from these studies will provide insight into chemical structures that mediate the binding and activation of receptor-mediated processes. Through biomolecular mimicry, the proposed studies will lead to more efficient design of ligands that will enhance nanocarrier delivery.
This project is jointly funded by the Biomaterials Program in the Division of Materials Research, the Established Program to Stimulate Competitive Research (EPSCoR), and the Polymers Program in the Division of Materials Research.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
