Doctor of Philosophy / Department of Chemistry / Stefan H. Bossmann / Cancer is one of the leading causes of death in the world. Billions of dollars are spent to
treat cancer every year. This clearly shows the need for developing improved treatment
techniques that are affordable to every person. Early diagnosis and imaging of tumors is equally
important for the battle against this disease. This dissertation will discuss new approaches for
discovering and developing novel detection and treatment techniques for cancer using organic
ligands, and Fe/Fe3O4 core/shell magnetic nanoparticles.
A series of o-phenylenediamine derivatives with nitro-, methyl- and chloro- substituents
were synthesized and studied their ability to act as anticancer agents by using steady-state,
UV/Vis-, and fluorescence spectroscopy. In the absence of zinc(II), intercalation with DNA is
the most probable mode of interaction. Upon addition of zinc(II), DNA-surface binding of the
supramolecular aggregates was observed. The interaction of the supramolecular (-ligand-Zn2+-)n
aggregates with MDA 231 breast cancer cells led to significant cell death in the presence of
UVA at λ=313 nm displaying their potential as anticancer agents.
Bimagnetic Fe/Fe3O4 core/shell nanoparticles (MNPs) were designed for cancer targeting
after intratumoral or intravenous administration. Their inorganic center was protected by
dopamine-oligoethylene glycol ligands. TCPP (4-tetracarboxyphenyl porphyrin), a fluorescent
dye, was attached to the dopamine-oligoethylene glycol ligands. These modified nanoparticles
have the ability to selectively accumulate within the cancerous cells. They are suitable candidates
for local hyperthermia treatment. We have observed a temperature increase of 11 ºC in live mice
when subcutaneously injecting the MNPs at the cancer site and applying an alternating magnetic
field The system is also suitable for Magnetic Resonance Imaging (MRI), which is a diagnostic
tool to obtain images of the tumors. Our superparamagnetic iron oxide nanoparticles have the
ability to function as T1 weighted imaging agents or positive contrasting agents. We were able to
image tumors in mice using MRI.
Various proteases are over-expressed by numerous cancer cell lines and, therefore, of
diagnostic value. Our diagnostic nanoplatforms, designed for the measurement of protease
activities in various body fluids (blood, saliva, and urine), comprise Fe/Fe3O4 core/shell
nanoparticles featuring consensus sequences, which are specific for the target protease. Linked to
the consensus sequence is a fluorescent organic dye (e.g. TCPP). Cleavage of the sequence by
the target protease can be detected as a significant increase in fluorescence occurring from
TCPP. We were able to correlate our diagnostic results with cancer prognosis.
| Identifer | oai:union.ndltd.org:KSU/oai:krex.k-state.edu:2097/13541 |
| Date | January 1900 |
| Creators | Samarakoon, Thilani Nishanthika |
| Publisher | Kansas State University |
| Source Sets | K-State Research Exchange |
| Language | en_US |
| Detected Language | English |
| Type | Dissertation |
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