Date of Award

Spring 5-12-2017

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Chemistry

First Advisor

Santimukul Santra (ssantra@pittstate.edu)

Second Advisor

Irene Zegar (izegar@pittstate.edu)

Third Advisor

Charles Neef (cneef@pittstate.edu)

Fourth Advisor

Petar Dvornic (pdvornic@pittstate.edu)

Fifth Advisor

Neil Snow (nsnow@pittstate.edu)

Keywords

Nanoparticles, Cancer, Polyester, Click Chemistry, Nanomedicine

Abstract

In this study, a synthetic polyester polymer was designed using polyethylene glycol, sorbitol, glutaric acid and 4-pentynoic acid as monomers. The synthesis was carried out using standard melt polymerization technique and catalyzed by Novozyme-435, an enzyme suitable for polyesterification of biocompatible compounds. The progress of the reaction was monitored with respect to time and vacuum exposure, with samples being subjected to standard characterization protocols. Polymers with high molecular weight and water solubility were chosen for further modification into folate-functionalized polymeric nanoparticles for targeted drug delivery to cancer cells. This was achieved by employing a solvent diffusion method, wherein the polymer can be simultaneously converted into water-soluble nanoparticles and therapeutic agents (Taxol) and imaging dyes (DiI) can be encapsulated. The efficacy of this delivery system was gauged by treating LNCaP and PC3 prostate cancer cells with the drug and dye-loaded nanoparticles and assessing the results of the treatment. The results were analyzed by cytotoxicity (MTT) assays, drug release studies, and confocal and fluorescence microscopy. The experimental results collectively show a nanoparticle that is biocompatible, target-specific, and successfully initiates apoptosis in an in-vitro prostate cancer cell model.

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