Integration of simultaneous and cascade release of two drugs into smart single nanovehicles based on DNA-gated mesoporous silica nanoparticles

Stimuli-responsive multidrug delivery systems need to be invented for clinical combination therapy by the controlled release behavior of each drug individually. A facile, effective, and universal platform was built for simultaneous and cascade release of two drugs from DNA-gated gold nanorod-embedded mesoporous silica nanoparticles (MSNs) functionalized with titanium(IV)-chelating phosphonates. Coordination chemistry is the first strategy for DNA capping through multivalent chelating interactions in drug delivery systems not only as a gatekeeper but also as a drug carrier. One drug was entrapped in the MSN pores, and the other drug intercalated within the capping duplex DNA. The two drugs were simultaneously released upon triggering of endonuclease degradation or photothermal dehybridization and were successively released upon first triggering of basic pH and subsequent triggering of photothermal heating. The designed native DNA-gated MSN delivery systems integrated a simultaneous and cascade release of two drugs into smart single nanovehicles for promising practical applications in targeted combination drug therapy.