Reversible stimuli-responsive controlled release using mesoporous silica nanoparticles functionalized with a smart DNA molecule-gated switch

We reported a novel reversible stimuli-responsive controlled-release system consisting of mesoporous silica nanoparticles (MSN) functionalized with a smart DNA molecule-gated switch. In this system, a unique sequential cytosine (C)-rich DNA as the smart molecule-gated switch was grafted on the mesoporous silica nanoparticles (MSN) surface. In the presence of Ag+ ions, the closer C-rich DNA could hybridize each other by the formation of C–Ag+–C structure based on metal-dependent pairs of two nucleobases, resulting in blocking of pores and packing of guest molecules. By a competitive displacement reaction, the duplex DNA with C–Ag+–C structure deformed into single-stranded DNA in the presence of thiol-containing molecules, such as dithiothreitol (DTT), which gave rise to uncapping and the subsequent release of the entrapped guest molecules. The reversible open and closed states of the DNA molecule-gated switch could be easily achieved by alternating addition of Ag+ linkers and DTT molecules. Our results demonstrated that the system had excellent loading amount (43 μmol g−1) and good controlled release behavior. Moreover, the system could enter the cells through endocytosis and showed a low cytotoxicity even with treatment at a high concentration (200 μg mL−1). We believe that the stimuli-responsive controlled MSN release system based on the smart molecule-gated switch could play an important role in the development intracellular delivery nanodevices.