SERS-based detection and quantification of cancer biomarkers in cells and tissue microarrays release_ap23d6hrybdk3pldqma2xresw4

Abstract

The need for early detection of cancer has resulted in the development of a number of molecular identification techniques that can screen for cancer biomarkers or cellular components indicative of a cancerous state. Biomarkers play a crucial role in cancer diagnosis and their identification and quantification can help monitor disease progression and therefore significantly contribute to clinical prognosis and to individualization and optimization of systemic therapy. Nanomaterial-based imaging systems provide the sensitivity, selectivity, and high multiplexing capability needed for molecular detection when leveraging the optical phenomenon of surface-enhanced Raman scattering (SERS). SERS is a vibrational spectroscopic technique that can be used to detect molecules present on or near the surface of plasmonic nanomaterials such as gold nanoparticles. The objective of this dissertation was to develop a SERS-based imaging tool for phenotype assessment of cancer cells and tissues by utilizing the optical properties of gold nanostars (i.e. gold nanoparticles (AuNPs) with a spherical core and sharp protruding spikes) together with the effective targeting ability of aptamers. It was hypothesized that gold nanostars would be able to provide excellent SERS enhancement factors that would enable the quantification of biomarker expression at the single cell level. However, toxicity of the nanoparticles is a critical issue that needs to be taken into consideration before their implementation in vitro. For this purpose, detailed multi-parametric assessment of gold nanoparticle toxicity was carried out in cancerous (glioblastoma cells, U-87) and healthy cells (human fibroblasts) where the effects of nanoparticle shape, surface chemistry, and size on cell toxicity and cellular uptake were assessed. The study demonstrated that gold nanostars can be effectively taken up by both cell types without inducing significant toxicity when capped by a suitable ligand. They were therefore considered to be less toxic when compared to other [...]
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