Iron Release Profile of Silica-Modified Zero-Valent Iron NPs and Their Implication in Cancer Therapy

To evaluate the iron ion release profile of zero-valent iron (ZVI)-based nanoparticles (NPs) and their relationship with lysosomes in cancer cells, silica and mesoporous silica-coated ZVI NPs (denoted as ZVI@SiO(2) and ZVI@mSiO(2)) were synthesized and characterized for the following study of cytotoxicity, intracellular iron ion release, and their underlying mechanisms. ZVI@mSiO(2) NPs showed higher cytotoxicity than ZVI@SiO(2) NPs in the OEC-M1 oral cancer cell line. In addition, internalized ZVI@mSiO(2) NPs deformed into hollow and void structures within the cells after a 24-h treatment, but ZVI@SiO(2) NPs remained intact after internalization. The intracellular iron ion release profile was also accordant with the structural deformation of ZVI@mSiO(2) NPs. Burst iron ion release occurred in ZVI@mSiO(2)-treated cells within an hour with increased lysosome membrane permeability, which induced massive reactive oxygen species generation followed by necrotic and apoptotic cell death. Furthermore, inhibition of endosome–lysosome system acidification successfully compromised burst iron ion release, thereby reversing the cell fate. An in vivo test also showed a promising anticancer effect of ZVI@mSiO(2) NPs without significant weight loss. In conclusion, we demonstrated the anticancer property of ZVI@mSiO(2) NPs as well as the iron ion release profile in time course within cells, which is highly associated with the surface coating of ZVI NPs and lysosomal acidification.