Synthesis and Characterization of Polymeric Materials as Sequestrants for Biological Applications

Abstract

To address the systemic toxicity attributable to doxorubicin (Dox) following targeted chemotherapy treatments for hepatocellular carcinoma, we explored drug-capture strategies using both DNA-functionalized substrates and synthetic polymeric materials. DNA-modified cotton substrates were prepared with and without using silane linkers and surprisingly, DNA-only modified substrates demonstrated comparable Dox capture efficacy to those functionalized with DNA and the control silane linker. DNA quantification revealed apparent increases in DNA concentration due to thermally induced denaturation during adsorption, suggesting the need for milder reaction conditions for future experiments. We also synthesized poly(methacrylic acid) (PMA) resins to electrostatically bind Dox at physiological pH. Comparative capture studies with uncharged PMA at low-pH conditions confirmed an 18-fold increase in Dox capture efficacy due to ionic interactions. Crosslink density and polymer flexibility also played pivotal roles, with more rigid materials demonstrating greater capture efficacy and more flexible materials exhibiting the opposite trend due to increased hydrophobicity. These results underscore the importance of tuning network rigidity and hydrophobicity in subsequent drug-capture material design. Finally, to explore alternatives to traditional antibiotics, we synthesized varied molecular weights of mannose-functionalized polynorbornenes and modified the polymer backbone with thiolated-mannose and thiolated-amine moieties. Our objective was to increase the antibacterial properties observed with unmodified glycopolymers by increasing glycan density to inhibit bacterial growth and separately, introducing cationic charges to disrupt bacterial membranes. Our approach used the oxo-norbornene derivative, a key procedural change as these materials are not widely explored for post-polymerization modification, particularly with biologically relevant molecules such as glycans and cationic compounds. While we observed partial functionalization of the polymer backbone at longer reaction times, we demonstrated that the backbone alkenes of these glycopolymers are amenable to thiol-ene chemistry. We also generated a set of materials with precise architecture that differed only in their pendant functionalities. Comprehensive biological assays will follow to assess the antimicrobial and hemolytic performances and determine the structure-activity relationships.