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Magnetic particles to control cellular signaling molecules

Posted on:2016-12-25Degree:Ph.DType:Thesis
University:University of FloridaCandidate:Monsalve, Adam GustavoFull Text:PDF
GTID:2471390017476943Subject:Biomedical engineering
Abstract/Summary:
Action at a distance, enabled by the usage of magnetic materials, proves a promising asset for biomedical applications. Unique properties exhibited by magnetic micro- and nanomaterials include such phenomena as the release of heat in an alternating applied magnetic field, the application of translational forces in a magnetic field gradient, and the potential for bioconjugation enabling specific functionality in both in vitro and in vivo..;For osteoarthritis patients, many biomolecules contribute to the progressive degradation of cartilage inducing inflammation of the joints, including the interleukins. Magnetic microparticles can scavenge these molecules from the joint space to both diagnose levels of that biomolecule and treat disorders resulting from excess concentrations. The present work shows the capacity for capturing Interleukin-1beta (IL- 1beta) in significant levels. In addition to depletion for therapeutic purposes, the level of depletion as a function of time was utilized to quantify unknown solutions of IL-1beta.;Transforming growth factor beta (TGF-beta), has wide-ranging implications in the body and can be a devastating molecule if presented to the incorrect cell at the incorrect time. Surface functionalization of the latent TGF-beta, to the surface of magnetic nanoparticles allowed for spatiotemporal control over the active state of the molecule, and therefore its ability to signal to cells. The surface energy delivered to the latent complex proved enough to release comparable amounts of biologically active TGF-beta to the same particles treated thermally to activate the complex. Additionally, the active form of TGF-beta was bound to the surface and shown to induce intracellular signaling, indicating the cytokine remained active when bound to the particle surface.;Aptamers, a novel class of macromolecules, show promise for clinical use due to ease of chemical synthesis, similar binding affinities to antibody molecules, and nonimmunogenicity.[ 1] Biological characterization of a novel aptamer targeting vascular endothelial growth factor receptor-2 (VEGFR2) showed binding to human endothelial cells. The aptamer, presented in a dimeric structure, showed the capacity to bind VEGF receptors on cells and activate downstream pathways, indicating potential for spatial control over vascularization. Additionally, magnetic particles surface functionalized with the VEGFR2 targeting aptamer were assessed for VEGFR2 phosphorylation.
Keywords/Search Tags:Magnetic, Particles, Surface, VEGFR2
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