Noble metal nanoparticles, especially those of gold and silver, exhibit extraordinary properties at the nanoscale. Their distinctive plasmonic characteristics make them highly valuable in a wide range of applications, including biosensing and therapeutic technologies. This research will be conducted within the Functional NanoBioMaterials group, which specializes in the synthesis of nanoparticles with specific optical characteristics for use in diverse fields such as surface-enhanced Raman scattering (SERS) spectroscopy, immunoassays, and theragnosis. The thesis pursues three main objectives: (i) diagnostics using SERS probes in the development of SERS-based lateral flow immunoassay (LFIA) sensors, (ii) immunophenotyping of tumor cells, and (iii) cancer bioimaging and therapy using hybrid bacteria-nanoparticle systems. To complete the first objective, a highly sensitive SERS-based digital lateral flow immunoassay is proposed for the detection of the SARS-CoV-2 nucleocapsid protein, achieving ultra-low detection limits and improved quantification compared to conventional methods. This method will significantly improve diagnostic accuracy and sensitivity, offering great potential for advanced infectious disease detection. The next objective will be carried out in collaboration with the Caruso Nanoengineering Group (CNG) at the University of Melbourne (Australia). It will demonstrate a dual-mode multiplex immunophenotyping approach combining SERS and flow cytometry using nanoprobes based on MPN-coated plasmonic nanoparticles. These nanoprobes enable highly sensitive and multiplexed detection of biomarkers while reducing signal interference and improving probe stability. It will be applied to detect EGFR and CD44 in HER14 cells, offering robust and reproducible results and holding great potential for diagnostics, therapeutic monitoring, and broader biomedical applications. Regarding the latter objective, bacteria-nanoparticle biohybrids will be developed for bioimaging and thermal therapy of EGFR-overexpressing cancers by attaching gold-based nanostructures to modified E. coli via the SpyTag/SpyCatcher interaction. These hybrid systems enable SERS imaging and photothermal therapy (PTT) of tumor cells by combining plasmonic nanoparticles with bacteria with targeting capabilities. This system aims to demonstrate the specific detection of cancer biomarkers and the efficacy of PTT in vitro, offering a flexible tool for future cancer diagnosis and therapy.
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