TitleDesign, synthesis, and utility of fuctionalized nanoscale amphiphilic macromolecules for biomedical applications
NameSparks, Sarah Marie (author), Uhrich, Kathryn E (chair), Seidel, Daniel (internal member), Warmuth, Ralf (internal member), Moghe, Prabhas V (outside member), Rutgers University, Graduate School - New Brunswick,
SubjectChemistry and Chemical Biology,
Polymers in medicine,
DescriptionPolymeric micelles are spherical assemblies of amphiphilic polymers widely studied for many biomedical applications. Nanoscale amphiphilic macromolecules (AMs) are novel amphiphilic polymers composed of an alkylated sugar backbone covalently linked to poly(ethylene glycol) (PEG). In aqueous solution, AMs self-assemble to form 10-20 nm micelles with critical micelle concentrations as low as 100 nM, making them more stable than other common micelles. In addition, the basic structure of AMs has multiple points of modification such that the polymer can be modified and evaluated for virtually any application. This work highlights the promise of functionalized AMs as a novel, versatile biomaterial. Carboxy-terminated AMs were previously shown to inhibit highly oxidized low- density lipoprotein (hoxLDL) uptake in macrophage cells. To gain a mechanistic understanding of this inhibition, a series of AMs were designed and synthesized by modifying the basic polymer structure to evaluate several characteristics including: amphiphilicity, PEG chain length, anionic charge location, type of anionic charge, number of anionic charges, rotational motion of the anionic group, and PEG architecture. The optimal AM for inhibiting hoxLDL uptake was determined to be one with a rigid, rotationally-restricted carboxylic acid within the hydrophobic portion of the polymer. Building upon previous work that showed AMs deliver cargo intracellulary, a series of cationic polymers were designed and synthesized for nucleic acid delivery. The cationic moiety was added within the hydrophobic component of the AMs such that when the cationic portion complexed with anionic nucleic acids, the nucleic acids would be localized in the micellar interior. Three cationic AMs were evaluated with varying surface charges. The polymer with the highest surface charge was the most effective at complexing with and delivering small interfering RNA to U87 glioma cells. Finally, without modification, AMs are capable of water-solubilizing hydrophobic drugs. This property can be applied to hydrophobic fluorescent nanocrystals, which are useful for biological imaging. In the last chapter, AMs were utilized to water-solubilize white light-emitting nanocrystals without altering the emission properties of the nanocrystals. By modifying the polymer structure to incorporate functionalities that can coordinate to the surface of the nanocrystals, smaller, water-soluble assemblies that maintain white light-emission were obtained.
NoteIncludes bibliographical references
Noteby Sarah Marie Sparks
CollectionGraduate School - New Brunswick Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.