Functional polymeric dialdehyde dextrin network capped mesoporous silica nanoparticles for pH/GSH dual-controlled drug release

Multi-stimulation responsive nanomaterial-based drug delivery systems promise enhanced therapeutic efficacy in cancer therapy. This work examines a smart pH/GSH dual-responsive drug delivery system by using dialdehyde dextrin (DAD) end-capped mesoporous silica nanoparticles (MSNs). Specifically, DAD was applied as a "gatekeeper polymer" agent to seal drug loads inside the mesoporous of MSNs via a pH-sensitive Schiff bond, whereas the formed DAD polymer shells were further cross-linked by GSH-sensitive disulfide bonds. Results revealed that the DAD gatekeeper polymer could tightly close the mesopores of MSNs to control premature drug release under physiological conditions and respond to acidic and GSH conditions to release the trapped drugs. Significantly, fluorescent microscopy observation and cytotoxicity studies indicated that drug-loaded nanoparticles could be rapidly internalized through a passive targeting effect to inhibit cancer growth. Taken together, these polymer-modified pH/GSH dual-responsive MSNs could be used as promising candidates for "on-demand" anticancer drug delivery applications.