A dual drug delivery platform based on thermo-responsive polymeric micelle capped mesoporous silica nanoparticles for cancer therapy

The combination of organic polymers and inorganic nanoparticles to design intelligent nanocarriers is of great significance for effective delivery of anticancer drugs to tumor cells for therapy. Herein, we have prepared a thermo-responsive micelle as a “gatekeeper” to attach on the surface of mesoporous silica nanoparticle (MSN) through disulfide bonds. DOX was encapsulated in both nanocarriers, resulting in a pH/redox/temperature responsive dual drug delivery platform (DOX@MSN-S2-F127-PCL@DOX, abbreviated as DMSFPD) with high loading capacity and excellent stimuli-responsive performance for cancer therapy. The cumulative release curve in vitro indicated that DOX could be controllably released from DMSFPD. With the elevated temperature at 40 °C, the uncapping ofF127-PCL250 (FP250) micelle from MSN after GSH stimulus and the shrinkage of FP250 micelle caused a fast release of DOX from both MSN and micelle, which greatly increased the drug concentration immediately. The intracellular uptake and cytocompatibility demonstrated that MSN-S2-F127-PCL250 (MSFP250) could be efficiently endocytosed and have shown favorable biocompatibility in both normal and tumoral cells. Cytotoxicity results illustrated that DMSFPD could significantly kill different kinds of cancer cells. Therefore, this dual drug delivery capping platform provides a new and promising strategy for cancer therapy.