Tracking the intracellular drug release from graphene oxide using surface-enhanced Raman spectroscopy

We have developed a graphene oxide (GO)-based nanoplatform simultaneously loaded with a chemical drug and Ag nanoparticles (NPs), and employed it to study the drug release from GO in living cells by surface-enhanced Raman spectroscopy (SERS). In our strategy, doxorubicin (DOX), a typical model anticancer drug, was loaded onto chemically prepared GO by means of π-π stacking, while the Ag NPs were covalently modified onto GO. After incubation of the DOX- and Ag NPs-loaded GO with Ca Ski cells for several hours, DOX will detach from the GO in an acidic environment due to the pH-dependent π-π interaction between DOX and GO. Real-time measurement of SERS signals of DOX using the GO loaded with Ag NPs as a SERS-active substrate allows us to monitor the process of the drug release inside the living cell. The SERS results reveal that DOX is initially released from the GO surface inside the lysosomes, then escapes into the cytoplasm, and finally enters the nucleus, while GO, the nanocarrier, remains within the cytoplasm, without entering the nucleus.