Formation of enzymatic/redox-switching nanogates on mesoporous silica nanoparticles for anticancer drug delivery

In this study, we demonstrate a simple approach to developing mesoporous nanohybrids via a process of preloading of an anticancer drug (doxorubicin, DOX) into mesoporous silica nanoparticles (MSN), followed by assembly with a kind of naturally-derived polymer (gelatin, cleavable by matrix metalloproteinase 2 overexpressed by tumor). The gelatin shell is then in situ crosslinked by degradable N,N'-bis(acryloyl)cystamine (BAC) to form enzymatic and redox switchable nanogates on the mesoporous nanoparticles. The nanohybrids displayed pH/redox/enzymatic sensitivity in DOX release under conditions mimicking tumor microenvironments. The nanocarriers can be effectively taken up by A549 cells (a carcinomic human alveolar basal epithelial cell line), resulting in a high DOX intracellular accumulation and an improved anticancer cytotoxicity when compared with free DOX, suggesting their potential as a nanoplatform for therapeutic delivery.