Gd-metallofullerenol nanomaterial as non-toxic breast cancer stem cell-specific inhibitor

Ying Liu; Chunying Chen; Pengxu Qian; Xuefei Lu; Baoyun Sun; Xiao Zhang; Liming Wang; Xingfa Gao; Han Li; Zhiyun Chen; Jinglong Tang; Weijie Zhang; Jinquan Dong; Ru Bai; Peter E. Lobie; Qingfa Wu; Suling Liu; Huafeng Zhang; Feng Zhao; Max S. Wicha; Tao Zhu; Yuliang Zhao

doi:10.1038/ncomms6988

Gd-metallofullerenol nanomaterial as non-toxic breast cancer stem cell-specific inhibitor

Ying Liu, Chunying Chen, Pengxu Qian, Xuefei Lu, Baoyun Sun, Xiao Zhang, Liming Wang, Xingfa Gao, Han Li, Zhiyun Chen, Jinglong Tang, Weijie Zhang, Jinquan Dong, Ru Bai, Peter E. Lobie, Qingfa Wu, Suling Liu, Huafeng Zhang, Feng Zhao, Max S. WichaTao Zhu, Yuliang Zhao

Houston Methodist

Research output: Contribution to journal › Article › peer-review

182 Scopus citations

Abstract

The contemporary use of nanomedicines for cancer treatment has been largely limited to serving as carriers for existing therapeutic agents. Here, we provide definitive evidence that, the metallofullerenol nanomaterial Gd@C₈₂ (OH)₂₂, while essentially not toxic to normal mammary epithelial cells, possesses intrinsic inhibitory activity against triple-negative breast cancer cells. Gd@C₈₂ (OH)₂₂ blocks epithelial-to-mesenchymal transition with resultant efficient elimination of breast cancer stem cells (CSCs) resulting in abrogation of tumour initiation and metastasis. In normoxic conditions, Gd@C₈₂ (OH)₂₂ mediates these effects by blocking TGF-β signalling. Moreover, under hypoxic conditions found in the tumour microenvironment, cellular uptake of Gd@C₈₂ (OH)₂₂ is facilitated where it functions as a bi-potent inhibitor of HIF-1 and TGF-β activities, enhancing CSC elimination. These studies indicate that nanomaterials can be engineered to directly target CSCs. Thus, Gd-metallofullerenol is identified as a kind of non-toxic CSC specific inhibitors with significant therapeutic potential.

Original language	English (US)
Article number	5988
Journal	Nature Communications
Volume	6
DOIs	https://doi.org/10.1038/ncomms6988
State	Published - Feb 2015

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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Liu, Y., Chen, C., Qian, P., Lu, X., Sun, B., Zhang, X., Wang, L., Gao, X., Li, H., Chen, Z., Tang, J., Zhang, W., Dong, J., Bai, R., Lobie, P. E., Wu, Q., Liu, S., Zhang, H., Zhao, F., ... Zhao, Y. (2015). Gd-metallofullerenol nanomaterial as non-toxic breast cancer stem cell-specific inhibitor. Nature Communications, 6, Article 5988. https://doi.org/10.1038/ncomms6988

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abstract = "The contemporary use of nanomedicines for cancer treatment has been largely limited to serving as carriers for existing therapeutic agents. Here, we provide definitive evidence that, the metallofullerenol nanomaterial Gd@C82 (OH)22, while essentially not toxic to normal mammary epithelial cells, possesses intrinsic inhibitory activity against triple-negative breast cancer cells. Gd@C82 (OH)22 blocks epithelial-to-mesenchymal transition with resultant efficient elimination of breast cancer stem cells (CSCs) resulting in abrogation of tumour initiation and metastasis. In normoxic conditions, Gd@C82 (OH)22 mediates these effects by blocking TGF-β signalling. Moreover, under hypoxic conditions found in the tumour microenvironment, cellular uptake of Gd@C82 (OH)22 is facilitated where it functions as a bi-potent inhibitor of HIF-1 and TGF-β activities, enhancing CSC elimination. These studies indicate that nanomaterials can be engineered to directly target CSCs. Thus, Gd-metallofullerenol is identified as a kind of non-toxic CSC specific inhibitors with significant therapeutic potential.",

author = "Ying Liu and Chunying Chen and Pengxu Qian and Xuefei Lu and Baoyun Sun and Xiao Zhang and Liming Wang and Xingfa Gao and Han Li and Zhiyun Chen and Jinglong Tang and Weijie Zhang and Jinquan Dong and Ru Bai and Lobie, {Peter E.} and Qingfa Wu and Suling Liu and Huafeng Zhang and Feng Zhao and Wicha, {Max S.} and Tao Zhu and Yuliang Zhao",

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AU - Liu, Ying

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AU - Sun, Baoyun

AU - Zhang, Xiao

AU - Wang, Liming

AU - Gao, Xingfa

AU - Li, Han

AU - Chen, Zhiyun

AU - Tang, Jinglong

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AU - Dong, Jinquan

AU - Bai, Ru

AU - Lobie, Peter E.

AU - Wu, Qingfa

AU - Liu, Suling

AU - Zhang, Huafeng

AU - Zhao, Feng

AU - Wicha, Max S.

AU - Zhu, Tao

AU - Zhao, Yuliang

PY - 2015/2

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N2 - The contemporary use of nanomedicines for cancer treatment has been largely limited to serving as carriers for existing therapeutic agents. Here, we provide definitive evidence that, the metallofullerenol nanomaterial Gd@C82 (OH)22, while essentially not toxic to normal mammary epithelial cells, possesses intrinsic inhibitory activity against triple-negative breast cancer cells. Gd@C82 (OH)22 blocks epithelial-to-mesenchymal transition with resultant efficient elimination of breast cancer stem cells (CSCs) resulting in abrogation of tumour initiation and metastasis. In normoxic conditions, Gd@C82 (OH)22 mediates these effects by blocking TGF-β signalling. Moreover, under hypoxic conditions found in the tumour microenvironment, cellular uptake of Gd@C82 (OH)22 is facilitated where it functions as a bi-potent inhibitor of HIF-1 and TGF-β activities, enhancing CSC elimination. These studies indicate that nanomaterials can be engineered to directly target CSCs. Thus, Gd-metallofullerenol is identified as a kind of non-toxic CSC specific inhibitors with significant therapeutic potential.

AB - The contemporary use of nanomedicines for cancer treatment has been largely limited to serving as carriers for existing therapeutic agents. Here, we provide definitive evidence that, the metallofullerenol nanomaterial Gd@C82 (OH)22, while essentially not toxic to normal mammary epithelial cells, possesses intrinsic inhibitory activity against triple-negative breast cancer cells. Gd@C82 (OH)22 blocks epithelial-to-mesenchymal transition with resultant efficient elimination of breast cancer stem cells (CSCs) resulting in abrogation of tumour initiation and metastasis. In normoxic conditions, Gd@C82 (OH)22 mediates these effects by blocking TGF-β signalling. Moreover, under hypoxic conditions found in the tumour microenvironment, cellular uptake of Gd@C82 (OH)22 is facilitated where it functions as a bi-potent inhibitor of HIF-1 and TGF-β activities, enhancing CSC elimination. These studies indicate that nanomaterials can be engineered to directly target CSCs. Thus, Gd-metallofullerenol is identified as a kind of non-toxic CSC specific inhibitors with significant therapeutic potential.

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Gd-metallofullerenol nanomaterial as non-toxic breast cancer stem cell-specific inhibitor

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