We investigated interfacial behaviors of erlotinib (EL) on gold nanoparticles (AuNPs) by means of Raman spectroscopy. The adsorption reactions and structures of EL on AuNP surfaces were examined by UV-Vis absorption spectroscopy and surface-enhanced Raman scattering (SERS). Density functional theory calculations were performed to estimate the energetic stabilities of the drug-AuNP composites. Among the binding units in EL, the acetylenic C equivalent to C group was calculated to be the most strongly binding on the AuNP cluster atoms, consistent with the SERS spectra. The concentration-dependent SERS spectra indicated that similar to 10(-5) M of EL exhibited the highest SERS signals. The attached EL appeared to desorb more efficiently with 2 mM glutathione than with cell culture media. The lack of a strong SERS signal of EL in the darkfield microscopy images of AuNP-EL complexes suggested almost complete desorption of EL inside cells. (C) 2014 Elsevier Inc. All rights reserved.