Nanoshells for Surface-Enhanced Raman Spectroscopy in Eukaryotic Cells: Cellular Response and Sensor Development

The application of gold nanoshells (NS) as a surface-enhanced Raman (SER) platform for intracellular sensing in NIH-3T3 fibroblast cells was studied by using a near-infrared Raman system. To show the feasibility of using these 151 +/- 5 nm sized solution-stable nanoparticles inside living cells, we investigated the uptake, cellular response, and the health of the cell population. We show that NS are taken up voluntarily and can be found in the cytosol by transmission electron microscopy (TEM), which also provides detailed information about location and immediate surrounding of the NS, The internalization into cells has been found to be independent of active cellular mechanisms, such as endocytosis, and can be suggested to be of passive nature. Uptake of NS into cells can be controlled, and cells show no increase in necrosis or apoptosis as a result; we show that NS-based intracytosolic SER spectra can be measured on biological samples using short acquisition times and low laser powers. We demonstrate its application using 4-mercaptobenzoic acid (4-MBA)-functionalized nanoshells as a pH sensor.