Abstract
Stimuli-responsive nanomaterials have been receiving much attention as drug delivery carriers, however understanding of multi-drug release from the carriers for efficient therapeutics is highly challenging. Here, we report a novel nanosystem, Janus particle Dox-CMR-MS/Au-6MP (Dox: doxorubicin, CMR: 7-hydroxycoumarin-3-carboxylate, MS: mesoporous silica, Au: gold, 6MP: 6-mercaptopurine) with opposing MS and Au faces, which can monitor intracellular dual-drug (Dox and 6MP) controlled release in real time based on fluorescence resonance energy transfer (FRET) and surface-enhanced Raman scattering (SERS). The FRET acceptor Dox is attached to CMR (as a FRET donor) conjugated MS with a pH-responsive linker hydrazone, and 6MP is conjugated to the Au surface through the gold-thiol interaction. As the Janus nanoparticle enters into tumor cells, the breakage of the hydrazone bond in an acidic environment and the substitution of glutathione (GSH) overexpressed in cancer cells give rise to the release of Dox and 6MP, respectively. Thus, the change of the CMR fluorescence signal and the SERS decrease of 6MP can be used to monitor the dual-drug release within living cells in real time. In addition, this work demonstrates the enhanced anticancer effect of the designed dual-drug loaded nanosystem. Therefore, the current study may provide new perspectives for the real-time study of intelligent multidrug delivery and release, as well as cellular responses to drug treatment.
Schematic representation of the Janus Dox/6MP NPs and the mechanism of real-time monitoring of dual drugs with pH/redox dual responsive release in living cells. The framework of MS is functionalized with CMR and the nanochannel walls are modified with Dox by the pH-responsive linker hydrazone. The Au surface is conjugated with 6MP by the gold-thiol bond. After entering tumor cells, the breakage of the hydrazone bond in an acidic environment and the overexpressed GSH trigger the release of Dox and 6MP, separately. The FRET and SERS on / off process can be used to monitor the dual-drug release within living cells in real time.
Cao, H.; Yang, Y.; Chen, X.; Shao, Z., Intelligent Janus nanoparticles for intracellular real-time monitoring of dual drug release. Nanoscale 2016, 8, (12), 6754-6760.
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