Graduation Semester and Year

2012

Language

English

Document Type

Dissertation

Degree Name

Doctor of Philosophy in Biomedical Engineering

Department

Bioengineering

First Advisor

Kytai Truong Nguyen

Abstract

With an increasing rate of cancers, the need for effective cancer management has led to the development of theranostic systems for diagnosis and therapy. Conventional techniques for cancer management have limited success due to inaccurate diagnosis and treatment side effects. Development of magnetic-based theranostic nanoparticles (MBTN) may overcome these limitations with the advantages of magnetic nanoparticles (MNPs) such as magnetic targeting, hyperthermia, and magnetic resonance imaging (MRI) contrast agents; and advantages of polymer coatings for carrying payloads and allowing bioconjugation for active targeting applications. Aim of this research was to develop multifunctional MBTNs for prostate cancer management. First, biodegradable photoluminescent polymers (BPLP)-coated iron oxide MNPs were developed, which were stable, well dispersed, and exhibited both a bright fluorescence in UV light and dark negative contrast in MRI. Moreover, these cytocompatible nanoparticles released most of the therapeutically effective drugs within 21 days. Prostate cancer cells also showed selective uptake of nanoparticles depending on cell type. Finally, the presence of magnetic field reinforced the uptake of nanoparticles as seen from in vitro cellular uptake and in vivo biodistribution study. Second, thermo-responsive polymer-coated MNPs (PMNPs) were formulated and conjugated with prostate cancer-specific R11 peptides for active targeting of drugs to prostate cancer cells only. The cytocompatible PMNPs also generated a dark negative contrast in MRI. Moreover, a higher uptake of R11-PMNPs was noticed compared to non-conjugated PMNPs. Preliminary in vivo studies showed that R11-PMNPs accumulated more in the tumor compared to non-conjugated PMNPs. Finally, novel thermo-responsive fluorescent polymer-coated MNPs (TFPMNPs) were developed by combining the principles from both BPLP-MNPs and PMNPs. Cytocompatible TFP-MNPs possessed temperature-dependent fluorescence and drug release. TFP-MNPs also exhibited a bright fluorescence in the prostate cancer orthotopic mouse model. Preliminary investigation on these nanoparticles (BPLPMNPs, PMNPs, and TFP-MNPs) in vivo and results from in vitro studies demonstrated their potential as multifunctional theranostic nanoparticles for various biological applications, including prostate cancer management.

Disciplines

Biomedical Engineering and Bioengineering | Engineering

Comments

Degree granted by The University of Texas at Arlington

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