Tumor-Marker-Mediated "on-Demand" Drug Release and Real-Time Monitoring System Based on Multifunctional Mesoporous Silica Nanoparticles

"On-demand" drug release can maximize therapeutic efficacy for specific states of malignancies and minimize drug toxicity to healthy cells. Meanwhile, there is lack of a real-time monitoring platform to accurately investigate the amount of anticancer drugs released, especially nonfluorescent ones. So it is significant to integrate both issues in one ideal drug delivery system. To achieve this, here we present a novel stimuli-responsive controlled drug delivery system toward the tumor marker survivin mRNA, using a real-time monitoring approach based on the fluorescence resonance energy transfer (FRET) strategy to quantify the process of drug release. First, 7-amino-4-methlcoumarin (AMCA) dye terminated short oligonucleotide (FlareA) will hybridize with fluorescein isothiocyanate (FITC) labeled long oligonucleotide (S1F), which contains a recognition element to a specific RNA transcript, to form a FRET pair capped on the pores of mesoporous silica nanoparticles (MSNs). Following a target-recognition reaction, the target with a longer strand displaces the FlareA strand to form a longer and more stable duplex with S1F, which leads to the removal of the capped oligonucleotide from the MSNs and triggers the release of the entrapped cargo while FRET between AMCA and FITC is broken. The relevant change in donor and acceptor fluorescence signal can be used to monitor the unlocking and release event in real-time. Further investigations have also demonstrated that this release system possesses the capacity of modulating the extent of drug release according to the cell states, giving the platform an equally broad spectrum of applications in anticancer therapy.