Multistage pH-responsive mesoporous silica nanohybrids with charge reversal and intracellular release for efficient anticancer drug delivery.

This study introduced multistage pH-responsive nanohybrids (MSN-hyd-MOP) based on mesoporous silica nanoparticles (MSNs) modified with polymers with charge-reversal property via an acid-labile hydrazone linker, which were applied as a drug delivery system loaded anticancer drugs. In this study, MSN-hyd-MOP nanohybrids were completely investigated for their synthesis, pH response, drug release behavior, cytotoxicity capability and endocytic behavior. Responding to the acidic extracellular microenvironment of solid tumor (pH 6.5), MSN-hyd-MOP nanohybrids exhibited surface charge-reversal characteristic from negative (-10.2 mV, pH 7.4) to positive (16.6 mV, pH 6.5). The model drug doxorubicin (Dox) was efficiently loaded within the channels of MSN-hyd-MOP (encapsulation efficiency about 87%). The increased acidity in endo-/lysosome promote Dox-loaded MSN-hyd-MOP (MSN-hyd-MOP@Dox) release Dox quickly. In vitro study revealed the drug delivery system had good biocompatibility and could deliver the payload to tumor cells. Overall, the described nanohybrids can be used as a potential anticancer drug delivery system.