Surface-Chemistry Effect on Cellular Response of Luminescent Plasmonic Silver Nanoparticles

[Image: see text] Cellular response of inorganic nanoparticles (NPs) is strongly dependent on their surface chemistry. By taking advantage of robust single-particle fluorescence and giant Raman enhancements of unique polycrystalline silver NPs (AgNPs), we quantitatively investigated effects of two well-known surface chemistries, passive PEGylation and active c-RGD peptide conjugation, on in vitro behaviors of AgNPs at high temporal and spatial resolution as well as chemical level using fluorescence and Raman microscopy. The results show that specific c-RGD peptide−α(v)β(3) integrin interactions not only induced endosome formation more rapidly, enhanced constrained diffusion, but also minimized nonspecific chemical interactions between the NPs and intracellular biomolecules than passive PEGylation chemistry; as a result, surface enhanced Raman scattering (SERS) signals of c-RGD peptides were well resolved inside endosomes in the live cells, while Raman signals of PEGylated AgNPs remained unresolvable due to interference of surrounding biomolecules, opening up an opportunity to investigate specific ligand–receptor interactions in real time at the chemical level.