Date of Award

Summer 7-10-2019

Document Type

Thesis

Degree Name

Master of Science in Chemistry (MSChem)

Department

Chemistry

First Advisor

Dr. Santimukul Santra

Second Advisor

Dr. Tuhina Banerjee

Third Advisor

Dr. Irene Zegar

Fourth Advisor

Dr. Jian Hong

Keywords

Nanoparticle, Cancer, Polyester, Biocompatible, Nanomedicine, Targeted Delivery

Abstract

In this study, a hyperbranched polyester co-polymer was designed using a proprietary monomer and diethylene glycol or triethylene glycol as monomers. The synthesis was carried out using standard melt polymerization technique and catalyzed by p-Tolulenesulfonic acid. The progress of the reaction was monitored with respect to time and negative pressure, with samples being subjected to standard characterization protocols. The resulting polymers were purified using the solvent precipitation method and characterized using various chromatographic and spectroscopic methods including GPC, MALDI-TOF, and NMR. We have observed polymers with a molecular weight of 29,643 kDa and 33,996 kDa, which is ideal to be used as a drug delivery system. Thus, these polymers were chosen for further modification into folate-functionalized polymeric nanoparticles for targeted drug delivery to LNCaP prostate cancer cells. We hypothesized that due to the 3D structure of the A2B monomer, we expect a pseudo-branched polymer that is globular in shape which will be ideal for drug carrying and delivery. We used a solvent diffusion method, wherein the polymer can be simultaneously converted into water-dispersible nanoparticles and therapeutic agents (doxorubicin) can be encapsulated into the polymeric nanocavities. The efficacy of this delivery system was gauged by treating LNCaP prostate cancer cells with the drug-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 was biocompatible, target-specific, and successfully initiated apoptosis in an in-vitro prostate cancer cell model.

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