Exploiting the Nanoparticle Plasmon Effect: Observing Drug Delivery Dynamics in Single Cells via Raman/Fluorescence Imaging Spectroscopy

Drug delivery systems (DDSs) offer efficient and localized drug transportation as well as reduce associated side effects. In order to better understand DDSs, precise observation of drug release and delivery is required. Here, we present a strategy, plasmonic-tunable Raman/fluorescence imaging spectroscopy, to track the release and delivery of an anticancer drug (doxorubicin) from gold nanoparticle carriers in real time at a single living cell level. A pH-responsive drug release profile was attained through the conjugation of doxorubicin (DOX) to the nanoparticle surface via a pH-sensitive hydrazone linkage. When DOX is bound to the surface of the gold nanoparticle, its surface-enhanced Raman spectrum can be seen, but its fluorescence is quenched. When released, due to the lysosomes' acidic pH, its Raman enhancement is greatly reduced, changing the acquired Raman spectrum and in turn allowing for the visualization of its fluorescence signal. The plasmonic-tunable Raman/fluorescence properties enabled the tracking of the DOX release and delivery process from the gold nanoparticle surface to the lysosomes of single living cells under the acidic pH change of their microenvironments. This technique offers great potential to follow the molecular mechanisms of drug delivery and release in living cells, as well as the cellular response to drug action.