The increasing number of reports about false positive or negative results from conventional cytotoxicity assays of nanomaterials (NMs) suggests that more reliable NM toxicity assessment methods should be developed. Here, we report a novel approach for nanotoxicity evaluation based on surface-enhanced Raman spectroscopy (SERS). Three model NMs were tested on two model cell lines and the results were validated by WST-1 cytotoxicity assay and annexin V-FITC/propidium iodide (PI) staining as apoptosis-necrosis assay. The localization of nanoparticles (NPs) in the cells and the cellular conditions upon NP incubation were visualized by transmission electron microscopy (TEM) and enhanced dark-field (EDF) microscopy. SERS revealed a broader view on the consequences of cell-NM interactions compared to the conventional cytotoxicity assays where only one aspect of toxicity can be measured by one assay type. The results suggest that SERS can significantly contribute to the cytotoxicity evaluation bypassing NM or assay component-related complications with less effort.

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Herein we report the detection and differentiation of plasmonic and non-plasmonic nanoparticles simultaneously administered to A549 lung epithelium cells using dark-field microscopy and hyperspectral imaging. Reflectance spectra-based hyperspectral mapping and image analysis allows for the effective quasi-quantitative identification of nanomaterials in cultured human cells.

There is an ongoing effort to obtain molecular level information from living cells using surface-enhanced Raman scattering (SERS) not only to understand changes of cellular processes upon exposure to external stimuli but also to decide the status of cells; whether they are healthy or abnormal. In our research effort, we investigate how much information can be obtained from living cells to use for decision making about the cellular processes using SERS. The undertaken studies include cytotoxicity assessment of the nanomaterials and differentiation of the healthy and cancer cells. In the first case, A549 (lung cancer) and HDF (human dermal fibroblast) cells were incubated with 50 nm gold nanoparticles (AuNP) and exposed to three different nanoparticles (Zinc oxide nanoparticles (ZnO NPs), titanium dioxide nanoparticles (TiO 2 ) and single walled carbon nanotubes (SWCNTs)) to perform SERS analysis and track the cellular response to these nanomaterials (NMs). After the principal component analysis on the spectral data, it was shown that the NPs exposed samples could be differentiated through SERS. In the second case, SERS spectra obtained from human kidney adenocarcinoma (ACHN), human kidney carcinoma (A-498) and non-cancerous human kidney embryonic cells (HEK 293) were used to diagnose metastatic, primary and non-cancerous cell lines. Linear discriminant analysis (LDA) based on principal component analysis (PCA) was applied to collected multidimensional SERS spectral data set to differentiate three different cell lines.

Surface-enhanced Raman scattering captures spectral information from living cells, improving our understanding of a cell's molecular status.