Scheme 1.

Schematic illustration of the differential intracellular process of ZVI@SiO₂ and ZVI@mSiO₂ NPs. ZVI@mSiO₂ NPs with the sealed silica shell resisted the lysosomal acidic environment and remained intact. The coating also compromised the efficiency of particle uptake. Only mild iron ion release occurred, which did not cause ROS induction in cancer cells. However, ZVI@mSiO₂ NPs with mesoporous silica shell were sensitive to the acidic lysosomal environment, which resulted in structural deformation, intracellular burst iron ion release, massive ROS production, and subsequent necrosis and apoptosis in cancer cells.