Novel pH-responsive biodegradable organosilica nanoparticles as drug delivery system for cancer therapy

Although the biodegradability of silica has been verified, the complete and safe excretion of mesoporous silica nanoparticles (MSNs) from the biological system still impede their clinical translation. Herein, novel pH-responsive biodegradable hollow mesoporous organosilica nanoparticles (PBHMONs) based on pH-responsive silsesquioxane were successfully prepared for efficient anti-cancer drug delivery. pH-responsive cleavable bridges containing acetal moieties were prepared and then inserted directly into the framework of the MONs and the hollow nanostructures were achieved by silica-etching chemistry (alkaline etching). PBHMONs exhibited particularly high drug loading capacities for drugs (DOX) owing to the hollow mesoporous structure, and a uniquely low premature leakage owing to π-π interactions. Moreover, the pH-responsive biodegradation of the PBHMONs in the weakly acidic microenvironment of tumor cells led to partial drug release, as well as potential enabling rapid excretion and preventing long-term retention/toxicity.