The design, synthesis, and characterization of porphyrin-based dendrimers for the detection and treatment of solid tumors
Pearson, Andrew Michael
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Porphyrins have demonstrated functionality as photodynamic therapy (PDT) photosensitizers and magnetic resonance (MRI) contrast agents. Many harmful side effects of current porphyrin-based drugs result from collection of the drug in healthy tissues. These unwanted side effects could be prevented by specific targeting of the drug to tumor tissue. Because of a porphyrin’s unparallel ability to chelate many different metals, and efficiently sensitize the formation of singlet oxygen, there is a demand for research in the development of improved porphyrin-based drugs. The enhanced permeability and retention (EPR) effect states that macromolecules can actively target tumor tissue versus healthy tissue based on the different characteristics of each tissue. The most significant of these properties states that macromolecules cannot enter healthy tissue, but the deformed vasculature of tumor tissue allows entry of macromolecules. This research presents the design and synthesis of a porphyrinic dendrimer for the detection, destruction, and specific targeting of solid tumors. The triazine-based convergent synthesis is mild, efficient, and overcomes many common difficulties encountered in dendrimer synthesis. The exact dendrimer structure is fully characterized, which will allow for future modifications to optimize it’s efficacy as a PDT and MRI drug candidate. Future work includes the incorporation of poly(ethylene)glycols (PEG)s, for added biocompatibility, water solubility, increased molecular size, and a longer circulation time in the plasma.