TY - JOUR
T1 - Iron release profile of silica-modified zero-valent iron nps and their implication in cancer therapy
AU - Yang, Li Xing
AU - Wu, Ya Na
AU - Wang, Pei Wen
AU - Su, Wu Chou
AU - Shieh, Dar Bin
N1 - Funding Information:
Funding: This research was funded by the Ministry of Science and Technology, Taiwan, grant number MOST 104-2314-B-006-063-MY3, MOST 106-2627-M-006-001, and MOST 107-2321-B-006-019.
Funding Information:
This work was supported by the Taiwan Protein Project (Grant No. AS-KPQ-105-TPP) and financially supported by the Center of Applied Nanomedicine, National Cheng Kung University, Featured Areas Research Center Program, Higher Education Sprout Project of the Taiwan Ministry of Education (MOE), and by grants from the Taiwan Ministry of Science and Technology (MOST 104-2314-B-006-063-MY3; MOST 106-2627-M-006-001; MOST 107-2321-B-006-019; and MOST 108-2314-B-006 -009 -MY3). We thank the technical services provided by ?the i-MANI Center of the National Core Facility for Biopharmaceuticals, Ministry of Science and Technology, Taiwan? as well as the technical service from the Instrument Development Center of the National Cheng Kung University.
Funding Information:
Acknowledgments: This work was supported by the Taiwan Protein Project (Grant No. AS-KPQ-105-TPP) and financially supported by the Center of Applied Nanomedicine, National Cheng Kung University, Featured Areas Research Center Program, Higher Education Sprout Project of the Taiwan Ministry of Education (MOE), and by grants from the Taiwan Ministry of Science and Technology (MOST 104-2314-B-006-063-MY3; MOST 106-2627-M-006-001; MOST 107-2321-B-006-019; and MOST 108-2314-B-006 -009 -MY3). We thank the technical services provided by “the i-MANI Center of the National Core Facility for Biopharmaceuticals, Ministry of Science and Technology, Taiwan” as well as the technical service from the Instrument Development Center of the National Cheng Kung University.
Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2019/9
Y1 - 2019/9
N2 - 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.
AB - 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.
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U2 - 10.3390/ijms20184336
DO - 10.3390/ijms20184336
M3 - Article
C2 - 31487938
AN - SCOPUS:85071752344
VL - 20
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1661-6596
IS - 18
M1 - 4336
ER -