By using near-infrared surface-enhanced Raman scattering (SERS) with 60 nm gold nanoparticles (Au-NPs) to probe the chemical composition inside single human osteosarcoma cells we have shown that the SERS intensity may increase by a factor of 3–6 times in different parts of the cells depending on the density of gold nanoaggregates within the probed volume after the cell is dehydrated. The cellular points of low-density gold nanoaggregates exhibit more significant increase of SERS signal levels, the cellular macrochemicals such as nucleic acids show conformational changes, and new components can be probed after the cell is completely dried. A comparative study between viable and apoptotic cells indicates that most of the Au-NPs that enter the living cell reside in the cytoplasm and around the nucleus, whereas glyoxal-induced apoptotic cells show relatively uniform distribution of Au-NPs and, interestingly, the presence of DNA fragments is detected throughout the cell, including the cell surface.

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