Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.727507
Title: Development and characterisation of a multifunctional peptide-based vector for delivery of miR-34a gene therapy to metastatic prostate cancer
Author: Loughran, Stephen
ISNI:       0000 0004 6425 0295
Awarding Body: Queen's University Belfast
Current Institution: Queen's University Belfast
Date of Award: 2017
Availability of Full Text:
Full text unavailable from EThOS. Thesis embargoed until 01 Mar 2022
Abstract:
The aim of this thesis was to develop a peptide-based gene delivery system capable of delivering plasmid miR-34a to metastatic prostate cancer cells. The arginine-rich, fusogenic peptide known as RALA was used as the basis of the gene delivery vector. Polyethylene glycol 5K (PEG5K) was conjugated to the C-terminus of the RALA peptide (RALA-P) in order to improve peptide pharmacokinetics in vivo and promote tumour accumulation by the EPR effect. RALA was combined with RALA-P at various w/w ratios in order to identify which ratio provided optimal results in vivo. At w/w 6:8, the RALA/RALA-P conglomerate resulted in a significant increase in tumour accumulation and significantly reduced accumulation in off-target organs. In order to further improve tumour specificity, PEG5K was bound to RALA via an MMP2/9-cleavable linker (RALA-c-P) resulting in further increase in transgene expression at w/w 8:6 in the tumour site. The capacity for miR-34a to slow cancer growth rate and reduce metastatic potential in prostate cancer cell lines was verified both in vivo and in vitro. miR-34a was subsequently delivered to prostate cancer xenografts using RALA/RALA-c-P nanoparticle system resulting in reduced growth and increased survival.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.727507  DOI: Not available
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