Abstract
Gold deposition with diagonal angle towards boehmite-based nanostructure creates random arrays of horse-bean-shaped nanostructures named gold-nanofève (GNF). GNF generates many electromagnetic hotspots as surface-enhanced Raman spectroscopy (SERS) excitation sources, and enables large-area visualization of molecular vibration fingerprints of metabolites in human cancer xenografts in livers of immunodeficient mice with sufficient sensitivity and uniformity. Differential screening of GNF-SERS signals in tumours and those in parenchyma demarcated tumour boundaries in liver tissues. Furthermore, GNF-SERS combined with quantum chemical calculation identified cysteine-derived glutathione and hypotaurine (HT) as tumour-dominant and parenchyma-dominant metabolites, respectively. CD44 knockdown in cancer diminished glutathione, but not HT in tumours. Mechanisms whereby tumours sustained HT under CD44-knockdown conditions include upregulation of PHGDH, PSAT1 and PSPH that drove glycolysis-dependent activation of serine/glycine-cleavage systems to provide one-methyl group for HT synthesis. HT was rapidly converted into taurine in cancer cells, suggesting that HT is a robust anti-oxidant for their survival under glutathione-suppressed conditions.
Highlights
Gold deposition with diagonal angle towards boehmite-based nanostructure creates random arrays of horse-bean-shaped nanostructures named gold-nanofève (GNF)
Scanning electron microscopic (SEM) images showed a random array of the GNF substrate, which is named after the anisotropic shape of the Au nanostructure, as it resembles the shape of horse beans, and is distinct from spheroid GNC15
SEM (Fig. 1c, d) revealed that the interparticle space between Au nanoparticles formed by the deposition angle of 80° is larger than that of 0°and 45°
Summary
Gold deposition with diagonal angle towards boehmite-based nanostructure creates random arrays of horse-bean-shaped nanostructures named gold-nanofève (GNF). GNF generates many electromagnetic hotspots as surface-enhanced Raman spectroscopy (SERS) excitation sources, and enables large-area visualization of molecular vibration fingerprints of metabolites in human cancer xenografts in livers of immunodeficient mice with sufficient sensitivity and uniformity. SERS imaging is a comprehensive technique for visualizing metabolic profiles at multiple different wave numbers, and requires only a modest laser excitation, which minimizes artificial oxidation of metabolites. These characteristics are useful in accurately determining biomarker metabolites in diagnosing cancer. Development of a highly sensitive SERS imaging modality that can cover a large area aids our understanding of the metabolic interplay between cancer cells and surrounding tissues and assists in objective and automated identification of tumour (T) boundaries in tissues[9,10]. Non-target differentiation of such signals in T and parenchyma (P) helped identify T boundaries in frozen tissue sections by means of automated a Spectrograph
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