Type of Document Dissertation Author Hollingsworth, Javoris Author's Email Address email@example.com URN etd-11162012-103236 Title Synthesis, Characterization, and Self-Assembly of Porphyrins Conjugated to Superparamagnetic Colloidal Particles for Enhanced Photodynamic Therapy Degree Doctor of Philosophy (Ph.D.) Department Chemistry Advisory Committee
Advisor Name Title Vicente, Graca Committee Chair Russo, Paul Committee Co-Chair Gilman, Doug Committee Member Spivak, David Committee Member Johnson, Crystal Dean's Representative Keywords
Date of Defense 2012-11-09 Availability unrestricted AbstractPorphyrins and their derivatives are often used as photosensitizers in photodynamic therapy (PDT), which is a noninvasive antitumor treatment. The photochemical process for PDT involves exciting a photosensitizing agent with visible light, which induces cytotoxicity in the presence of oxygen as a result of forming reactive oxygen species (ROS). The ROS are the responsible components for invoking cell death and destruction of tumors. Although this mechanism is an effective cancer therapeutic, it still has many shortcomings. One major challenge of PDT concerns improving the tumor selectivity and specificity of photosensitizers because porphyrins have nonspecific affinity to tumor cells. The discussed research introduces a potential drug delivery vehicle to enhance the efficacy of cancer therapeutics and overcome the aforementioned issues. Specifically, hybrid composite particles composed of superparamagnetic polypeptide-coated silica nanoparticles conjugated to porphyrins were designed to improve the mechanism of tumor cell destruction via controlled assembly and transport.
Along the path of developing these nanocomposites, porphyrin self-assembly was explored to understand the dynamics of porphyrins alone. A series of complementary experiments and analytical methods were used, including UV-Vis and fluorescence spectroscopy measurements, small angle X-ray scattering (SAXS), cryogenic transmission electron microscopy (cryo-TEM) and freeze-fracture transmission electron microscopy (FF-TEM). Whereas UV-Vis and fluorescence techniques enabled us to determine the type of aggregates formed, AUC and SAXS provided complementary details and information about the size of the assemblies in solution. Cryo-TEM and FF-TEM provided direct visualization of the aggregates.
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