Abstract
The detection and monitoring of circulating tumor cells (CTCs) in blood is an important strategy for early cancer evidence, analysis, monitoring of therapeutic response, and optimization of cancer therapy treatments. In this work, tailor-made membranes (MBSP) for surface-enhanced Raman spectroscopy (SERS)-based analysis, which permitted the separation and enrichment of CTCs from blood samples, were developed. A thin layer of SERS-active metals deposited on polymer mat enhanced the Raman signals of CTCs and provided further insight into CTCs molecular and biochemical composition. The SERS spectra of all studied cells—prostate cancer (PC3), cervical carcinoma (HeLa), and leucocytes as an example of healthy (normal) cell—revealed significant differences in both the band positions and/or their relative intensities. The multivariate statistical technique based on principal component analysis (PCA) was applied to identify the most significant differences (marker bands) in SERS data among the analyzed cells and to perform quantitative analysis of SERS data. Based on a developed PCA algorithm, the studied cell types were classified with an accuracy of 95% in 2D PCA to 98% in 3D PCA. These results clearly indicate the diagnostic efficiency for the discrimination between cancer and normal cells. In our approach, we exploited the one-step technology that exceeds most of the multi-stage CTCs analysis methods used and enables simultaneous filtration, enrichment, and identification of the tumor cells from blood specimens.
Highlights
Circulating tumor cells (CTCs) are shed from the cancerous mass of the primary tumor cells and may get into the peripheral blood and transfer to distant tissues causing expansion of the cancer in the metastasis form [1]
The current ‘gold standard method’ of CTC detection and enumeration is the CellSearch system (Veridex LLC) for the analysis of CTCs in metastatic breast [18], prostate [19], and colon cancer patients [20]. In this method ferromagnetic beads are coated with antibodies against the epithelial cellular adhesion molecule (EpCAM), immunostained with fluorescently labeled anti-cytokeratin (CK, an epithelial intermediate filament), anti-CD45 antibodies, stained with DAPI (4,6-diamidino-2-phenylindole, a nuclear stain), and counted by automated cell image capture and analysis even from a 7.5 mL blood sample [21]
In our approach we offer a simple method that is optimal for CTC isolation, enrichment, detection, and molecular analysis
Summary
Circulating tumor cells (CTCs) are shed from the cancerous mass of the primary tumor cells and may get into the peripheral blood and transfer to distant tissues causing expansion of the cancer in the metastasis form [1]. Most of the presented SERS-based methods of CTC analysis require an enrichment step of a few CTCs from the blood and an extra labelling strategy for preparation, e.g., Raman reporter or peptides encoded NPs and/or tumor cells pre-labelled with NPs [29], which increases the cost and time of analysis. Even though many efficient SERS supports have been developed [38,39], there are some disadvantages associated with them, e.g., low stability over time, and inability to perform in situ measurements and sample mapping To avoid these problems, new production strategies of SERS platforms should be developed in order to Nanomaterials 2019, 9, 366 introduce SERS techniques to standard biomedical and analytical applications. The presented strategy may lead to development of new tools in CTC therapy
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