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Effects of Hydroxyapatite-Iron Oxide Nanocomposite Against Human Glioblastoma Cells

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Title: Effects of Hydroxyapatite-Iron Oxide Nanocomposite Against Human Glioblastoma Cells
Author(s): Pernal, Sebastian
Advisor(s): Uskokovic, Vuk
Contributor(s): Engelhard, Herbert H; Khetani, Salman R; Uskokovic, Vuk
Department / Program: Bioengineering
Degree Granting Institution: University of Illinois at Chicago
Degree: MS, Master of Science
Genre: Masters
Subject(s): Nanoparticles, nanocomposite, cancer, magnetic hyperthermia, glioblastoma, hydroxyapatite, iron oxide nanoparticles
Abstract: Cancer is the second leading cause of death in the United States and few treatments offer a panacea for all the various types of cancer that exist. Certain superparamagnetic iron oxide nanoparticles (SPIONs) are FDA-approved as contrast agents in magnetic resonance imaging while the potential applications for SPIONs are numerous. One such application is magnetic hyperthermia (MH) where alternating magnetic fields applied to SPIONs generate heat. MH in treating cancer would cause cancer cells to deteriorate from the inside without the use of strong chemotherapeutics. SPION effectiveness is hindered by the low uptake in cancer cells and the generation of reactive oxygen species that cause harm to the healthy cells in the body. In early studies, healthy, primary mouse kidney and lung fibroblasts had an increased uptake of iron oxide nanoparticles (IONs) versus human brain cancer cells (E297 and U87) and mouse osteosarcomas (K7M2.) Hydroxyapatite (HAP), the primary ceramic in our bones, offers a solution to SPION delivery. HAP particles are commended as a biomaterial for their biodegradability and biocompatibility, and their use as a nonviral transfection agent. Dispersing IONS in HAP nanoparticles could increase the uptake in cancer cells and minimize the risk to healthy cells. The goal of this work is the construction and characterization of a hydroxyapatite-iron oxide nanocomposite (HAP-ION) usable as a device for magnetic hyperthermia, minimizing the risk to healthy cells and increasing their uptake in cancer cells. HAP-IONs retain the superparamagnetic nature of IONs, have increased uptake in cancer cells versus their ION counterparts, reduce cancer cell viability and primary cancer spheroid migration, and maintain the viability of healthy human mesenchymal stem cells (hMSCs). Further analysis of actin cytoskeleton revealed that healthy hMSCs have a reduced anisotropy in their cytoskeleton arrangement after the uptake of IONs, while primary cancerous cells have an increased anisotropy in cytoskeleton arrangement after the uptake of IONs. Nanocomposites of hydroxyapatite and IONs open a new avenue to cancer therapies that utilize MH.
Issue Date: 2016-11-28
Type: Thesis
URI: http://hdl.handle.net/10027/21574
Rights Information: Copyright 2017 Pernal, Sebastian
Date Available in INDIGO: 2019-02-18
Date Deposited: December 2
 

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