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

• Published in: International journal of molecular sciences 2019-09, Vol.20 (18), p.4336
• Main Authors: Yang, Li-Xing, Wu, Ya-Na, Wang, Pei-Wen, Su, Wu-Chou, Shieh, Dar-Bin
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Biocompatibility; Cancer therapies; Carcinogenesis; Carcinogens; Cell Line, Tumor; Cells, Cultured; Cytotoxicity; Drug Liberation; Ferrous ions; Human body; Humans; Investigations; Iron; Iron - pharmacology; Iron - therapeutic use; Lysosomes - drug effects; Lysosomes - metabolism; Male; Metal Nanoparticles - adverse effects; Metal Nanoparticles - chemistry; Mice; Mice, Inbred NOD; Mice, SCID; Model testing; Mutagenesis; Nanoparticles; Neoplasms, Experimental - drug therapy; Oral cancer; Oxidation; Oxidative stress; Protective coatings; Proteins; Reactive Oxygen Species - metabolism; Silica; Silicon dioxide; Silicon Dioxide - chemistry; Structure-activity relationships
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20184336

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 and ZVI@mSiO ) were synthesized and characterized for the following study of cytotoxicity, intracellular iron ion release, and their underlying mechanisms. ZVI@mSiO NPs showed higher cytotoxicity than ZVI@SiO NPs in the OEC-M1 oral cancer cell line. In addition, internalized ZVI@mSiO NPs deformed into hollow and void structures within the cells after a 24-h treatment, but ZVI@SiO NPs remained intact after internalization. The intracellular iron ion release profile was also accordant with the structural deformation of ZVI@mSiO NPs. Burst iron ion release occurred in ZVI@mSiO -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 NPs without significant weight loss. In conclusion, we demonstrated the anticancer property of ZVI@mSiO 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.