Abstract
Chemotherapy is one of the most commonly used systematic treatments for cancer, in which the drug release process is a key factor for drug delivery. In the present study, a real-time monitoring system for intracellular dual-drug controlled release based on fluorescence resonance energy transfer (FRET) and surface-enhanced Raman scattering (SERS) has been developed. The system consists of Janus nanoparticles possessing opposed mesoporous silica (MS) and gold (Au) faces. Anticancer drug doxorubicin (Dox) and dyecoumarin derivative (CMR), which served as FRET acceptor and donor, were conjugated to nanochannels of MS by a pH-responsive linker hydrazon and the framework of MS, respectively, while another anticancer drug 6- mercaptopurine (6MP) was conjugated to the Au side by disulfide bond. With the entry of Janus nanoparticle into tumor cells, the breakage of hydrazon at acidic environment and the substitution of glutathione (GSH) overexpressed in most cancer cells gave rise to the release of Dox and 6MP, respectively. Thus, the changes of fluorescence signal of CMR and the SERS decrease of 6MP could be used to real time monitor dual-drug release within living cells. Our work also showed that synergistic anticancer effect of these two drugs was achieved compared with single drug. Our study outlines a nanosystem for real- time tracing two drugs in living cells at the same time. Such system may open up new perspectives to real-time study of intelligent drug delivery and release in living cells, as well as the cellular responses to drug treatment.
Fig 1. Real-time monitoring Dox released from Janus CMR/Dox-MS/Au-6MP in Hela cells by confocal microscopy. Scale bar, 50 μm.
Fig 2. Real-time Raman spectra monitoring 6MP released from Janus CMR/Dox-MS/Au-6MP in Hela cells incubated with 5 mM glutathione ethyl ester (GSH-OET).
Cao, H.; Yang, Y.; Shao, Z., Bimodal real-time monitoring and dual responsive drug release based on Janus mesoporous silica-Au nanoparticles. Nanomedicine-Nanotechnology Biology and Medicine 2016, 12, (2), 484.
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