We describe a versatile approach for functionalizing core-shell Ag@SiO 2 nanoparticles for live-cell imaging. The approach uses physical adsorption and does not need covalent linkage to synthesize antibody-based labels. The surface orientation is not controlled in this approach, but the signal enhancement is strong and consistent. Antibodies were then attached using a non-covalent process that takes advantage of biotin-avidin affinity. Metal-enhanced nanoparticles doped with rhodamine B were used as the luminescent reporter. The enhancement of rhodamine B was between 2.7 and 6.8 times. We demonstrated labeling of CD19+ Ramos B lymphocytes and CD4+ HuT 78 T lymphocytes using anti-CD19 and anti-CD4 nanocomposite labels, respectively. This physical adsorption process can accommodate a variety of fluorophore types, and has broad potential in bioanalytical and biosensing applications.