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Title: Inorganic nanoparticle-oligonucleotide conjugates for bio-sensing and therapeutics
Author: Vilela, Patrick
ISNI:       0000 0004 7656 1947
Awarding Body: University of Southampton
Current Institution: University of Southampton
Date of Award: 2017
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In recent years, advances in conjugation techniques have allowed for the development of a vast range of hybrid materials nanomaterials with biomolecules. The use of hybrid nanomaterials has improved the imaging, treatment and diagnostics of specific biological processes. In this project, the main aim was to explore the uses of nanoparticle-oligonucleotide conjugates for biomedical applications. Gold nanoparticle-DNA probes for the intracellular detection of Vimentin mRNA were synthesized. These probes showed great target specificity and biocompatibility. Additionally, by means of light sheet microscopy, the three-dimensional visualization of Vimentin mRNA expression in tissue was performed in order to allow a deeper understanding of spatial and temporal expression events in wounded tissue. Furthermore, gold nanoparticles were also conjugated with siRNA sequences for the knockdown of SMAD3 gene in order to reduce the overproduction of TGF-β. This hybrid material showed efficient delivery of siRNA duplexes into both human and mice cells, with minimal toxicity. Upon applying the gold nanoparticle-siRNA silencing probes in in vivo murine models, preliminary results via photography and histological analysis pointed to a reduction of scar tissue formation. Finally, the conjugation of lanthanide upconversion nanoparticles and oligonucleotide sequences was performed for the successful development of a FRET type of sensor. This sensor was aimed for the detection of mRNA biomarkers of prostate cancer and Alzheimer's disease. Using graphene oxide as an electron acceptor, the nanoparticle-DNA conjugates specifically detected the presence of the target mRNA biomarker in low concentrations, both in blood plasma and cell lysate solutions.
Supervisor: Kanaras, Antonios Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available