Specific Interaction of Tricyclic Antidepressants with Gold and Silver Nanostructures as Revealed by Combined One- and Two-Photon Vibrational Spectroscopy

We report two-photon excited nonresonant surface-enhanced hyper Raman scattering (SEHRS) spectra of tricyclic antidepressant (TCA) molecules during their interaction with biocompatible gold nanostructures and with silver nanostructures. The SEHRS spectra of amitriptyline, desipramine, and imipramine are compared with surface-enhanced Raman scattering (SERS) spectra on both kinds of nanoparticles, obtained with excitation at 532 and 785 nm. The SEHRS spectra of the TCA molecules show several intense contributions by infrared-active vibrations. Combining SEHRS with SERS therefore enables a comprehensive vibrational characterization of the interaction of the molecules with the nanostructures. SEHRS and SERS data indicate that the molecules interact with the silver nanostructures mainly via their ring moiety. In contrast, in the interaction with gold, the methylaminopropyl side chain plays a very important role, along with parts of the ring system. It is possible to obtain the spectra of the molecules with near-infrared excitation and with gold nanoparticles in cell culture media. The spectral signatures of the drug molecules collected at low pH values characteristic of late endosomal stages or of acidified tissues are very stable and show only small changes in the interaction of the TCA with the gold nanoparticles. The results will help to develop tools for the characterization of new nanoparticle-based drug delivery platforms in real biological environments