Abstract
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@SiO2 and ZVI@mSiO2) were synthesized and characterized for the following study of cytotoxicity, intracellular iron ion release, and their underlying mechanisms. ZVI@mSiO2 NPs showed higher cytotoxicity than ZVI@SiO2 NPs in the OEC-M1 oral cancer cell line. In addition, internalized ZVI@mSiO2 NPs deformed into hollow and void structures within the cells after a 24-h treatment, but ZVI@SiO2 NPs remained intact after internalization. The intracellular iron ion release profile was also accordant with the structural deformation of ZVI@mSiO2 NPs. Burst iron ion release occurred in ZVI@mSiO2-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@mSiO2 NPs without significant weight loss. In conclusion, we demonstrated the anticancer property of ZVI@mSiO2 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.
Highlights
Based on reports from GLOBOCAN, cancer burden had risen to 18.1 million new cases and 9.6 million cancer deaths worldwide in 2018 [1]
zero-valent iron (ZVI) NPs fully covered with silica and mesoporous silica-coated zero-valent iron nanoparticles (ZVI NPs) were synthesized according to the protocols described by Ta-I Yang et al and Yu-Shen Lin et al for iron releasing effect against cancer cells study [31,32]
Because this research focused on the lysosomal interaction of ZVI NPs within ZVI-sensitive cells, the OEC-M1 cell line was applied as the model in this study
Summary
Based on reports from GLOBOCAN, cancer burden had risen to 18.1 million new cases and 9.6 million cancer deaths worldwide in 2018 [1]. Innovative nanomedicine, which has emerged recently, has shown several promising advantages over conventional cancer therapies, including early detection, improved treatment efficacy, and early diagnosis of cancer. A QSAR mechanistic interpretation to bridge the mutagenesis and carcinogenesis has been proposed [9,10]. Such NPs have been reported to kill cancer cells through oxidation therapy. Reactive oxygen species (ROS) are generated selectively in cancer cells for killing them while sparing healthy cells. Iron oxide (Fe3O4) NPs show the ability to selectively kill cancer cells through the induction of proapoptotic genes and tumor suppressor genes [11]. ROS production has been extensively observed for serial chemotherapeutic compounds, including vinblastine, cisplatin, and paclitaxel [14,15]
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