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Magnetic glyco-nanoparticles: A new tool to detect bacteria, cancer and atherosclerosis

Posted on:2011-06-23Degree:Ph.DType:Dissertation
University:Michigan State UniversityCandidate:El-Boubbou, KheireddineFull Text:PDF
GTID:1444390002458153Subject:Chemistry
Abstract/Summary:
Rapid and sensitive detection of pathogenic bacteria, cancer, and atherosclerotic plaques is critical for the prevention of such diseases and bioterrorism. To address these issues, we developed a magnetic iron oxide glyco-nanoparticle (MGNP)-based system as novel "detecting and imaging" vehicle with unique properties. In fact, there is an urgent need for an effective method for microbial decontamination and rapid pathogen detection without time consuming cell culturing. We proved that MGNPs can be utilized not only for fast pathogen detection, but also for strain differentiation and efficient pathogen decontamination. Using MGNPs, we were able to detect the presence of the bacterium Escherichia coli (E. coli) within five minutes as well as remove up to 88% of the microbe. Moreover, three different E. coli strains were easily identified using two MGNPs highlighting its potentials in bio-sensing. These results gave us great confidence to apply MGNPs for cancer detection. The development of simple and effective techniques to identify reliable detection methods and to delineate the fine characteristics of cancer cells can have great potential impacts on cancer diagnosis and treatment. We demonstrated the utilization of MGNP nanocomposites not only to detect and differentiate cancer cells but also to quantitatively profile their carbohydrate bindings by magnetic resonance imaging (MRI). Using an array of MGNPs, a range of cells including closely related isogenic tumor cells, cells with different metastatic potential and malignant vs normal cells were readily distinguished based on their respective "MRI signatures". As the interactions between glyco-conjugates and endogenous lectins present on cancer cell surface are crucial for cancer development and metastasis, the ability to characterize and unlock the glyco-code of individual cell lines can facilitate both the understanding of the roles of carbohydrates as well as the expansion of diagnostic and therapeutic tools for cancer. Building on the success of bacterium and cancer detection, we moved on to examine the utility of MGNPs for in vivo atherosclerotic detection. Despite the significant progress in cardiology, there remain large unmet needs to detect atherosclerotic plaques. One of the major causes of such dramatic event is "inflammation" which occurs during early onset of the disease leading to over-expression of cell-adhesion receptors. Our proposed work is based on the knowledge that hyaluronic acid (HA) is upregulated in atherosclerotic lesions and its principal cell-adhesion receptor, CD44 is involved in several atherogenic processes. Thus, we engineered hyaluronic-coated magnetic nanoparticles (HA-MGNPs) to non-invasively image atherosclerotic plaques via MRI. Today's nanotechnologies are enabling better detection and diagnosis systems with great therapeutic potentials. Tomorrow is likely to bring a full understanding of the "cell-NP bioconversation" where major problems relating to detection will be solved translating insights from the "nano-world" into clinical practice.
Keywords/Search Tags:Cancer, Detect, Atherosclerotic plaques, Magnetic
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