Design, synthesis and characterization of functionalized SCK nanoparticles and functionalized biocompatible surfaces: Construction platforms for nanoparticle assembly and biomacromolecule immobilization.

摘要

This dissertation focuses on the design, synthesis and characterization of biotin-functionalized shell crosslinked knedel-like (SCK) nanoparticles, biotin-functionalized polymer brush surfaces, and their utilization as construction platforms for the study of streptavidin-mediated nanoparticle assembly.; SCKs are a class of nano-objects, originating from the self-assembly of amphiphilic block copolymers. Their synthesis and functionalization were accomplished beginning from the synthesis of block copolymers via living radical polymerization techniques, and extending to supramolecular assembly and polymer modification reactions. The regioselective placement of biotin units on the surface of SCK nanoparticles was achieved via two synthetic methods: mixed micelle formation with chain-end biotinylated block copolymers and their non-biotinylated analog followed by shell crosslinking reactions; and post-preparation functionalization reactions of SCKs with biotinylated molecules. Both methods enabled facile control of the degree of biotinylation. The resulting SCK nanoparticles were characterized thoroughly and the bioavailability of the biotin moieties present on the SCK surface was determined. These biotinylated SCK nanoparticles were used as building blocks for the preparation of streptavidin-mediated nanoparticle assemblies upon well-defined biotinylated substrates.; Chain-end biotinylated polymer brushes served as well-defined substrates for nanoparticle assembly. These functionalized polymer brush surfaces were prepared by a grafting-from technique utilizing nitroxide mediated polymerization (NMP). Functionalized initiators were synthesized and covalently immobilized on the surface in patterns by contact molding that allowed for the preparation of nano-patterned polymer brush surfaces via NMP. The biotinylated polymer brush surfaces were characterized thoroughly and used to immobilize streptavidin. Subsequent attachment of biotinylated SCKs led to the formation of layered, bio-synthetic materials through biotin/streptavidin interactions. The degree of biotinylation on both polymer brush surface and on the SCK nanoparticle was optimized to achieve the maximum amount of SCK attachment. In situ determination of the amount of proteins and nanoparticles adsorbed on the polymer brush surface provided further insight into the surface-immobilized ligand-receptor interactions.