We propose the combination of alkyne-tag and surface-enhanced Raman scattering (SERS) spectroscopy to perform
highly-sensitive and selective drug imaging in live cells. Gold nanoparticles are introduced in lysosomes through
endocytosis as SERS agents, and the alkyne-tagged drugs are subsequently administered in cells. Raman microscopic
observation reveals the arrival of drug in lysosome through enhanced Raman signal of alkyne. Since the peak of alkyne
appears in Raman-silent region of biomolecules, selective detection of drugs is possible without background signal of
endogenous molecules. From endocytosed gold nanoparticles in living HeLa cells, we observed distinct Raman signal
from alkyne-tagged inhibitor of lysosomal enzyme.