IR nanospectroscopy to decipher drug/metal nanoparticle interactions: Towards a better understanding of the spectral signal enhancement and its distribution

[Display omitted] •SERS and tapping AFM – SEIRA studies of the drug/metal nanoparticle interaction.•Strong AFM-SEIRA signal enhancement on the metal nanoparticle mono-layers.•The nature of the drug/metal mono-layer interaction drawn in the AFM-SEIRA maps. In this study, detailed considerations of the interactions appearing at drug/metal nanoparticle interfaces in micro- and nanoscale were performed. Application of the well-known surface-enhanced Raman spectroscopy (SERS) reveals information of how gefitinib, a drug approved in non-small cell lung cancer therapy, connects to the silver and gold nanoparticles (AgNPs and AuNPs, respectively). Such knowledge is important in the context of using the resulting conjugates to increase the effectiveness of cancer therapy. The received data were extended by the nanoscale analysis using atomic force microscopy in combination with the surface-enhanced infrared spectroscopy (AFM-SEIRA) in tapping mode. This allows to better visualize the discussed interaction with ultra-high spatial resolution even reaching the size of the particular nanoparticle (∼15 nm). It should be noted, that the metal nanoparticle mono-layer was enough to enhance the obtained AFM-SEIRA signal, which for the conventional surface-enhanced vibrational techniques would be unattainable. Moreover, since the surface enhancement phenomenon observed in the AFM-SEIRA technique is not fully understood the comparison between this effect and the signal reinforcement in SERS was performed. The drawn conclusions suggest the complementarity of both applied techniques and try to prove the statement that the intensity AFM-SEIRA maps reveal the nature of the drug/metal nanostructure interaction.