Developing Low Fouling Peptides and Zwitterionic Materials for Biomedical Applications

Abstract

This dissertation is a compilation of efforts aimed at developing mixed charge and zwitterionic materials to prevent biofouling in biomedical applications. Peptides are considered for use as natural low fouling materials due to their biocompatibility, diverse chemical properties, well-defined sequence, and biodegradability. Low fouling peptide sequences were rationally designed from known zwitterionic principles and biomimetically designed from the examination of human protein surfaces found in nature. The peptide sequences glutamic acid/lysine (EK) and asparagine (N) were identified as displaying resistance to nonspecific protein adsorption. The low fouling sequence EK was further applied to several biomedical applications including multifunctional self-assembled monolayers on a gold surface, stealth coatings on gold nanoparticles, and biodegradable EK-poly(lactic-co-glycolic) acid (EK-PLGA) drug delivery nanocarriers. Importantly, the EK sequence can be extended with functional peptide sequences (such as RGD for specific cell targeting) without the need for complex chemical conjugation. In addition to rational and biomimetic peptide design, a combinatorial screening method was explored to facilitate the testing of thousands of peptide sequences for low protein adsorption. Finally, zwitterionic polymers were explored to form particles for mucus-penetrating applications.