Portland State University. Department of Chemistry
Scott M. Reed
Term of Graduation
Date of Publication
Doctor of Philosophy (Ph.D.) in Chemistry
Cancer -- Photochemotherapy, Photochemotherapy
1 online resource (2, xxiii, 241 pages)
An underlying problem in Photodynamic Therapy (PDT) is low selectivity of photosensitizers currently being used for the treatment of tumors. This thesis is focused on developing new PDT drugs and is divided into two parts. The first chapter describes a method for selective delivery of the photosensitizers to the tumor site by conjugating porphyrins to an aptamer for the targeted PDT. To achieve this, a novel synthesis of 2'-porphyrin-modified uridine was developed. The 3'-H-phosphonate derivatives of both 2'-porphyrin and 2'-dithiaporphyrin modified uridine were also synthesized. The 3'41-phosphonate derivative of 2'-porphyrin-modified uridine was conjugated to a 19-mer DNA and to a 3l-mer aptamer that binds to under-glycosylated mucin 1 (uMUC1) glycoprotein, a well known tumor marker. The uMUC1 aptamer-porphyrin conjugate has potential applications for various tumor-targeted PDT. Potential applications of internally modified 2'-porphyrin 3'-H-phosphonate could be in the synthesis of various other aptamer-porphyrin conjugates or in creating porphyrin arrays on DNA scaffold by using automated solid phase synthesis.
The second part of the thesis describes the functionalization of gold nanoparticles with phospholipids. The idea behind this effort is to pave the way for future applications for the functionalization of bilayer gold nanoparticles with aptamer-porphyrin conjugates that could play dual roles for selective delivery of drugs and PDT. Both natural and synthetic phospholipids were used to synthesize gold nanoparticles coated with various types of phospholipid bilayers. Bilayer gold nanoparticles were converted to hybrid bilayer gold nanoparticles by partial thiol exchange. TEM image analysis showed only small changes in size by varying phospholipids in hybrid bilayer gold nanoparticles. The stabilities of bilayer and hybrid bilayer gold nanoparticles were tested with potassium cyanide and iodine. Results showed that the stability of various types of phospholipid-coated bilayer gold nanoparticles can be tuned by using partial alkanethiol exchange. Stable gold nanoparticles were obtained by exchanging hydrophobic alkanethiol for various types of phospholipid-coated bilayers gold nanoparticles, which forms a submonolayer on the gold surface with a gold: 1-decanethiol ratio of 21:1. The stable hybrid bilayer gold nanoparticles could find applications in micropatterning and formation of solid supported lipid bilayers for biosensor design.
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Sitaula, Sarita, "Synthesis of Aptamer-Porphyrin Conjugate for Photodynamic Therapy & Synthesis and stability of mixed thiol/lipid coated Gold Nanoparticles" (2009). Dissertations and Theses. Paper 6132.