Folate conjugated gold nanoparticles for surface-enhanced Raman imaging and theranostics on healthy and cancer human cells selective targeting of human cancer cells

Since its discovery, Surface Enhanced Raman Scattering (SERS) has been employed for the spectroscopic study and detection of molecules with a relevant role in biology [1,2]. More recently, the application of SERS-active nanostructures as spectroscopic “antennas” inside biological cells has proved to be a simple way to perform spectroscopic imaging of living tissues [3]. When dealing with biology, an interesting task for biophysics is to find ways to distinguish between healthy and cancer cells. Moreover, much interest has lately risen around the concept of “theranostics”, i.e. combining diagnostics with therapy, the latter to perform selectively on cancer cells without damaging the healthy ones [4]. When based on plasmonics, theranostics is often performed combining SERS and photothermal bleaching. Here we will present a biocompatible system based on gold nanoparticles (Nps) functionalized with the Raman active bifunctional linker 4-aminothiophenol. This molecule bounds covalently to the gold Np via the S-H moiety, and exposes the amminic NH2 group for further conjugation. This functional group is exploited for the binding of folic acid, a biomolecule with an essential role in cell reproduction. Our system can be considered a nanobiovector, as it is capable of targeting a specific kind of cell and locate in its proximity and/or inside it. Since cancer cell show many more receptors for folic acid than healthy cells, as they reproduce more quickly, the nanovectors will target cancer cells much more efficiently [5]. We will present SERS and microscopic characterization of this system. The interaction of our nanobiovector with different cell cultures will be explained, and proofs of selective targeting and eventual internalization in cells will be shown. The presence of SERS-active Nps allows for performing Raman imaging witnessing the position of the nanovector with respect to the cell (see Fig.1). We will also illustrate a SERS-based screening method that allows for distinguishing sick and healthy cell with an easy and quick measurement.