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Title: Intracellular delivery of self-assembling osteogenic nanoparticles
Author: Chambers, Philip
ISNI:       0000 0004 6424 5058
Awarding Body: Queen's University Belfast
Current Institution: Queen's University Belfast
Date of Award: 2017
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The aim of this research was to develop efficacious, peptide based nanoparticles that could be used as deliverable therapeutics to osteoprogenitor cells, increasing the rate of osteogenesis for use in the treatment of non-union fractures. The non-viral delivery vector RALA was developed within our research group and formed the delivery vehicle of choice. The first chapter of this thesis focuses on whether RALA was capable of creating nanosized hydroxyapatite (HA) nanoparticles with the optimal physiochemical and morphological characteristics for increased cellular uptake, and if they had the potential to affect the early markers of osteogenesis. The second chapter focused on further development of these particles, and through the addition of silica into the hydroxyapatite lattice (SiHA), facilitated the addition of a fluorescent tag for the purposes of interrogating the intracellular delivery of RALA/HA particles. A more involved and in depth study on the pro-osteogenic potential of RALA/SiHA was analysed with studies focusing on the genomic and proteomic levels of osteogenic markers Finally, the last experimental chapter focused on the newest generation of therapeutic treatments, microRNAs. MiR-26a was identified as an important regulator in osteogenesis and as such gene therapy nanoparticles consisting of RALA/plasmid DNA encoding for miR-26a was developed and delivered to MSCs with the effects on the osteogenic and angiogenic markers interrogated.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available