A facile way to synthesize dual-drug delivery nanocarrier for highly efficient therapy and tracing of intracellular drug release

Abstract

Dual-drug delivery systems designed for effective therapy is receiving much attention in cancer treatment, however, monitoring of the stimuli-responsive multi-drug release dynamics in living cells is still challenging. Here, a dual drug nanocarrier has been successfully synthesized using functionalized carbon nanotubes (CNTs). To obtain effective combination therapy, CNTs are used for loading dual drugs, that is, 6-thioguanine (6TG) and doxorubicin (DOX).By using label-free surface enhanced Raman scattering (SERS) and fluorescence techniques, the release dynamics of the loaded two kinds of drugs can be traced in living cells. In this nanocarrier, 6TG was conjugated to the surfaces of gold-silver core-shell nanoparticles (Au@Ag NPs). Release of 6TG can be triggered by glutathione (GSH). DOX was loaded onto CNTs surfaces via π–π stacking, which exhibits a pH-responsive release behavior. To investigate the intracellular traceable delivery performance of this nanocarrier, the dual drug loaded nanocarrier was incubated with living HeLa cells. Experimental results indicated that this dual drug nanocarrier can effectively enter into HeLa cells. And the release of 6TG and DOX were triggered by the substation of GSH and the acidic environment of lysosomes, respectively. By recording the real-time SERS and fluorescence signals of dual-drug inside HeLa cells, we can successfully monitor the dynamic process of intracellular drug release. Moreover, the combination of 6TG and DOX exhibited a synergistic effect to enhance the efficacy of cancer therapy. This kind of dual drug nanocarrier presents a new perspective for the design of smart multi-drug delivery systems for cancer therapy.