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dc.contributor.advisorBradley, Marken
dc.contributor.advisorVendrell Escobar, Marcen
dc.contributor.authorGarcía Guzmán, Claudia Maríaen
dc.date.accessioned2018-03-22T10:26:47Z
dc.date.available2018-03-22T10:26:47Z
dc.date.issued2017-11-30
dc.identifier.urihttp://hdl.handle.net/1842/28902
dc.description.abstractThe diagnosis of cancer in early stages is an unmet clinical need, especially in view that current treatments for cancer cannot address metastatic disease. Cancer aberration processes are associated to an increase in the production of reactive oxygen species (ROS). Chemical probes that can specifically detect these species are potentially useful as medical diagnostics and research tools for cancer imaging. One of the aims of my thesis was the design and synthesis of the activatable fluorescent probes based on small molecule fluorophores modified with chemically reactive moieties. The activation of these moieties by defined targets (e.g. ROS) results in the activation of the fluorophore and subsequent emission of a fluorescent signal. Two libraries of fluorescence probes for the detection of ROS have been designed and synthesised: 1) hydrocyanine-based probes as silent fluorophores that can be activated with superoxide ions, 2) coumarin-based hydrogen peroxide probes with red-shifted fluorescent properties and different boronate activatable groups for hydrogen peroxide sensing. We have performed in vitro assays to evaluate the fluorescence response of our probes as well as experiments in relevant live cells to assess their application for detection of ROS in live cells with molecular resolution. Moreover, cancer cells also overexpress Epidermal Growth Factor Receptors (EGFR). Surface-enhanced Raman scattering (SERS) nanotags that can recognize specifically EGFR receptors in cells are promising tools for the enhanced diagnosis of cancer. Two near-infrared cyanine Raman reporters were synthesized with a carboxylic group that was conjugated to cysteamine for derivatization of gold nanoparticles (AuNPs). This work was performed in the CSIR-NIIST (Kerala, India), where I did a 3-month PhD placement. I conjugated the cyanine reporters to spherical AuNPs of 40 nm diameter, and measured their Raman intensity and stability. The best SERS nanotags were selected for encapsulation with PEG and subsequently derivatization with anti-EGFR-EP22 antibodies. In vitro characterization of the SERS nanotags was performed: SERS and absorbance spectra, electron microscopy images as well as SERS imaging experiments in A549 lung cancer cells.en
dc.language.isoen
dc.publisherThe University of Edinburghen
dc.relation.hasversionGarcia-Guzman, C., Fernandez, A., Avlonitis, N., Bradley, M., & Vendrell, M. Red- Fluorescent Activatable Probes for the Detection of Hydrogen Peroxide in Living Cells. Combinatorial Chemistry & High Throughput Screening, 19 (5), 353-361. (2016).en
dc.subjectfluorescenceen
dc.subjectcoumarinen
dc.subjectreactive oxygen speciesen
dc.subjectImagingen
dc.subjectmacrophageen
dc.subjectinflammationen
dc.subjectdiagnosisen
dc.subjectcanceren
dc.subjectgold nanoparticlesen
dc.subjectRaman Imagingen
dc.subjectorganic synthesisen
dc.subjectTricarbocyaninesen
dc.subjecthydrocyaninesen
dc.titleOptical probes for enhanced targeting of canceren
dc.typeThesis or Dissertationen
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnamePhD Doctor of Philosophyen
dc.rights.embargodate2100-12-31
dcterms.accessRightsRestricted Accessen


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