Date on Senior Honors Thesis

5-2016

Document Type

Senior Honors Thesis

Department

Biology

Degree Program

College of Arts and Sciences

Author's Keywords

pancreatic cancer; nanoparticles; liposomes; photoacoustic

Abstract

Theranostic nanoparticles are emerging as a novel mechanism for detecting and treating cancer. Due to the difficulties in detection and treatment of pancreatic cancer, these particles could serve within this unique niche. In this study, a Syndecan-1 ligand was utilized to increase tumor specificity of fluorescent dye encapsulated liposomes which were evaluated as a potential theranostic nanoparticle for pancreatic adenocarcinoma. Their diagnostic capabilities and specificity to pancreatic adenocarcinoma were determined in vitro using immunocytochemistry and in vivo using multi-spectral optoacoustic tomography (MSOT). Immunocytochemistry showed that liposomes preferentially bound and released their contents into cells expressing high levels of Insulin-Like Growth Factor 1 Receptor. In an orthotopic pancreatic cancer mouse model, the liposomes preferentially targeted the pancreatic tumor with little off-target binding in the liver and spleen. Peak accumulation of the liposomes in the tumor occurred at 8 h post-injection. MSOT imaging was able to provide high-resolution 3D images of the tumor and liposome location. Ex vivo analysis showed that non-targeted liposomes accumulated in the liver suggesting that specificity of the liposomes for pancreatic adenocarcinoma was due to the presence of the Syndecan-1 ligand. Syndecan-1 tagged liposomes specifically target pancreatic adenocarcinoma both in vitro and in vivo. Once bound, the liposomes released the dye in vitro as indicated by red fluorescence of DNA-bound propidium iodide. The therapeutic drug-delivering capabilities of Syndecan-1 liposomes remain to be tested.

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