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Title: Micro-particles as cellular delivery devices
Author: Alexander, Lois Meryl
ISNI:       0000 0004 2729 0095
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2009
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Narrowly dispersed amino-functionalised polystyrene microspheres, with a range of diameters, were successfully synthesised via emulsion and dispersion polymerisation. Fluorescent labelling allowed cellular translocation to be assessed in a variety of cell lines and was found to be very high, but controllable, whilst exhibiting no detrimental effect on cellular viability. In order to fully determine the mode of microsphere uptake, “beadfected” melanoma (B16F10) cells were studied using both chemical and microscopic methods. Uptake was found to be wholly unreliant upon energetic processes, with microspheres located cytoplasmically and not encapsulated within endosomes, an important characteristic for delivery devices. In order to demonstrate the effective delivery of exogenous cargo mediated by microspheres, short interfering (si)-RNAs were conjugated to beads and investigated for the gene silencing of enhanced green fluorescent protein (EGFP) in cervical cancer (HeLa) and embryonic (E14) stem cells. EGFP knockdown was found to be highly efficient after 48 – 72 hours. Dual-functionalised microspheres displaying a fluorophore (Cy5) and siRNA allowed only those cells beadfected with the delivery vehicle (and thus containing siRNA) to be assessed for EGFP expression, yielding an accurate assessment of microsphere-mediated gene silencing. In addition, by manipulation of the microsphere preparation conditions, micro-doughnuts and paramagnetic microspheres were produced and their cellular uptake assessed. Paramagnetic microspheres were found to enter cells efficiently and were subsequently used to bias the movement of beadfected cells in response to an externally applied magnet, while micro-doughnuts were found to exhibit cell selective properties and were noted to traffic specifically to the liver in vivo.
Supervisor: Bradley, Mark. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: multifunctionalized microspheres ; fluorescent probes ; in vitro sensing ; cellular uptake