Structure-Dependent and Glutathione-Responsive Biodegradable Dendritic Mesoporous Organosilica Nanoparticles for Safe Protein Delivery

The design of smart nanocarriers that could recognize and differentiate cancer cells and normal cells is of great importance in drug delivery. Here we report the first example of cancer cell-specific degradable dendritic mesoporous organosilica nanoparticles (DDMONs). A unique pore structure-dependent glutathione (GSH)-responsive degradation behavior is revealed: the degradation rates of two nanoparticles with different pore sizes are similar in normal cells ("leveling effect"), while large-pore DDMONs show a faster degradation rate than small-pore nanoparticles in cancer cells with relatively high intracellular GSH levels ("differentiating effect"). The cancer cell-specific degradability and concomitant cargo release lead to efficient protein delivery toward cancer cells but reduced cytotoxicity toward normal cells.