Harnessing Functionalized Polysaccharides for Medical and Dental Applications

Abstract

Polysaccharides are an important class of biomolecules with many different biological functions and unique properties, thus it is unsurprising that polysaccharides are heavily researched as materials solutions in medicine and dentistry. This dissertation explores the potential of harnessing inherent and well-understood biological properties of polysaccharides, using chemical and materials modification techniques to create clinically useful systems for medical and dental challenges. Engineered polysaccharides systems were prepared and characterized, including starch nanoparticles with control of particle size, charge, loading, and attachment of functional molecules, and glycocalyx-mimetic polymer brushes. These systems were applied as a diagnostic aid for dental caries, as an anti-bacterial treatment, and in targeting tumor-associated macrophages. In the first application, fluorescent cationic (+5.8±1.2 mV) starch nanoparticles (size 101±56 nm) were prepared to target and adhere to early caries lesions to facilitate optical detection, test lesion activity, and monitor the impact of remineralization treatments in vitro. In the second application, similarly designed starch nanoparticles (size 440±58 nm) were loaded with antibacterial copper nanoparticles (6-7nm size, ~0.35% loading) to create a system which targets bacteria electrostatically and by their enzymatic metabolic processes. This system showed high antibacterial efficacy (3-log and 7-log bacterial reductions for S. aureus and B. subtilis, respectively, for copper nanoparticle dose of 17 µg/ml). The final application demonstrated high positive predictive value (>0.8 for M2 over M1) for cellular binding of glycocalyx-mimetic mannose-coatings with M2-polarized tumor-associated macrophages, with potential applications in cancer diagnostics and therapeutics. These examples highlight the utility of modified polysaccharides in the design of clinically useful systems in medicine and dentistry.