Surface enhanced Raman microimaging allows for screening single cells with different folate binding capabilities

In the last few decades, the development of novel spectroscopic techniques, often combining a very high sensitivity with huge spatial resolution, allowed the possibility of investigating down-scaled phenomena, as for example biochemical and biophysical processes in living systems. Surface Enhanced Raman Spectroscopy (SERS) is one of the most established techniques in this framework [1]. SERS is based on the plasmonic resonance of metal nanostructures: the collective electronic excitation at the metal surface can indeed be excited by light and give rise to the localization of strong electromagnetic fields close to the nanoparticle surface, which can be used for spectroscopy. In the past years, SERS has allowed to reach not only the threshold of single molecule vibrational spectroscopy [2], but also the implementation of devices in the field of biosensing, capable of detecting specific biomolecules at very low concentration by means of Raman spectroscopy [3]. Moreover, the implementation of SERS-labelled nanomaterials, such as functionalized metallic nanoparticles, paved the way for the application of these systems in the emerging field of nanomedicine [4]. Much interest has lately risen, indeed, around the concept of “theranostics”, i.e. combining diagnostics with therapy, the latter to perform selectively on cancer cells without damaging the healthy tissue [4]. Plasmonics-based theranostics is often designed combining SERS and photothermal bleaching. One of the open problems in biomedicine is the early detection of cancer, i.e. the capability of reveal the presence of the disease when it is not yet advanced. Addressing this problem, we designed a biocompatible system based on gold nanoparticles functionalized with the Raman active bifunctional linker 4-aminothiophenol and further conjugated with 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 on the folate receptors, on the cell membrane [5]. Folic acid receptors are generally overexpressed in many types of cancer cells, as these reproduce more frequently then ordinary ones [6]. The presence of folate receptors on the membrane strongly depends on the physiology of the cell line considered. In this presentation, we will show that the high specificity of our system allowed us not only to target cancer cells, but also to be able to distinguish different cell lines based on their level of expression of folate receptors [5].