Doctor of Philosophy (PhD)
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Cancer, Cell membrane, magnetic fields, nanoparticles, drug delivery
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Today, cancer is the world’s deadliest disease. Despite significant progress to find a cure, especially over the last decade, with immunotherapy rapidly becoming the state of the art, major open questions remain. Each successful therapy is not only limited to a few cancers but also has relatively low specificity to target cancer cells; although cancer cells can indeed be eradicated, many normal cells are sacrificed as collateral damage. To fill this gap, we have developed a class of multiferroic nanostructures known as magnetoelectric nanoparticles (MENs) that can be used to enable externally controlled high-specificity targeted delivery and release of therapeutic drugs on demand. First, the underlying physics of MENs was studied, as it relates to different externally applied sequences of a.c and d.c. magnetic fields to facilitate (i) high-specificity targeting driven by a physical force rather than antibody matching, (ii) a delivery mechanism that enhances cellular uptake (via nanoelectroporation) of therapeutic drugs across the cellular membrane of cancer cells only, and (iii) an externally controlled mechanism that releases the therapeutic drug on-demand. Secondly, the application of MENs as a nuclear magnetic resonance (NMR) nanoprobe was explored. The intrinsically coupled ferromagnetic and ferroelectric phases allowes the nanoparticle to be used as sensitive nanoprobe detectors of biological cells; based on the knowledge that the cellular membrane is an electrically charged medium which creates an ideal environment for MENs to distinguish between cancer and normal cells. Lastly, through in-vivo and in-vitro studies, MENs were used as drug delivery vehicle capable of crossing the blood brain barrier (BBB) and delivering recently discovered MIA690 peptide drug (via nanoelectroporation) to glioblastoma multiforme (GBM) brain cancer cells. Glioblastomas are tumors that arise from astrocytes in the brain; that are highly malignant and reproduces quickly due to their large network of blood vessels. In the following study, we report the binding efficacy of MIA690 to magnetoelecric nanoparticles as well as present an unprecedented targeted and on-demand release to glioblastoma cells through special sequences of a.c. and d.c. magnetic fields. The potential therapeutic and diagnostic impact of MENs for future medicine is beyond the scope of this study, as MENs can be used to treat any type of cancer.
Stimphil, Emmanuel, "Technobiology Paradigm in Nanomedicine: Treating Cancer with MagnetoElectric Nanoparticles" (2017). FIU Electronic Theses and Dissertations. 3546.
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