UCLA

Cationic polymers are of broad interest in the biotechnology sector due to their potential use in drug conjugation, tissue engineering, gene delivery, water purification and chelation, and stimuli-responsive materials. Of particular interest in designing cationic polymers is control over their pKa—allowing for the presentation of a positive charge at specific pH, which is dependent on molecular weight, connectivity, and pendant group identity of the polymer. In this dissertation, we designed and synthesized a series of smoking-inspired monomers and polymers based on pyrrolidine, piperidine, and tocopherol—utilizing copolymerization and other polymer chemistry strategies to vary their molecular weight, dispersity, hydrophilicity/hydrophobicity, charge density, and pKa. These polymers are designed to mimic certain chemical structures present in tobacco alkaloids or other smoking-related compounds that have implications in human health. In this work, we explore the utility of amine-based polymers within and beyond the scope of innate immunity—playing important roles in solving bioengineering and tissue engineering problems. Exposure to certain chemical factors present in tobacco and smoking-related compounds leads to the elevated risk and greater symptom severity of several autoimmune conditions. While this link has remained mechanistically unclear, the presence of protein/DNA immune complexes in systemic lupus erythematosus (SLE) has been designated as an important marker of disease severity, seen more prevalently in smokers vs. never-smokers. The smoking-inspired polymer library developed in this study is used to mimic the features of these immune complexes. Investigation of these polymeric materials complexed with negatively-charged biological macromolecules shows notable differences in complex formation, biophysical structure, and subsequent innate immune activity. These results provide further evidence of the role of biophysical complex structure in innate immune activity, and the role that tobacco’s chemical structures may play in exacerbating disease. Additional work explores the interaction of DNA with cigarette smoke in vitro—demonstrating the formation of visible clew-like precipitates upon DNA exposure to cigarettes. These pellets, which resemble the precipitates formed by the condensation of oppositely-charged biomacromolecules, demonstrate a level of biophysical ordering and immune activity seen in immunomodulatory DNA complexes.