Gd-metallofullerenol nanomaterial as non-toxic breast cancer stem cell-specific inhibitor
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@C 82 (OH) 22 , while essentially not toxic to normal mammary epithelial cells,...
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Published in | Nature communications Vol. 6; no. 1; p. 5988 |
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Main Authors | , , , , , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
London
Nature Publishing Group UK
23.01.2015
Nature Publishing Group Nature Pub. Group |
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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@C
82
(OH)
22
, while essentially not toxic to normal mammary epithelial cells, possesses intrinsic inhibitory activity against triple-negative breast cancer cells. Gd@C
82
(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@C
82
(OH)
22
mediates these effects by blocking TGF-β signalling. Moreover, under hypoxic conditions found in the tumour microenvironment, cellular uptake of Gd@C
82
(OH)
22
is facilitated where it functions as a bi-potent inhibitor of HIF-1α 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.
A metallofullerenol nanomaterial, Gd@C
82
(OH)
22
, was shown to inhibit growth of several solid cancers in preclinical models and yet exhibit low toxicity. Herein the authors show that Gd@C
82
(OH)
22
functions as an inhibitor of breast cancer stem cell function via blocking TGF-β and HIF-1α signalling, while sparing normal tissue. |
---|---|
AbstractList | 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@C
82
(OH)
22
, while essentially not toxic to normal mammary epithelial cells, possesses intrinsic inhibitory activity against triple-negative breast cancer cells. Gd@C
82
(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@C
82
(OH)
22
mediates these effects by blocking TGF-β signalling. Moreover, under hypoxic conditions found in the tumour microenvironment, cellular uptake of Gd@C
82
(OH)
22
is facilitated where it functions as a bi-potent inhibitor of HIF-1α 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.
A metallofullerenol nanomaterial, Gd@C
82
(OH)
22
, was shown to inhibit growth of several solid cancers in preclinical models and yet exhibit low toxicity. Herein the authors show that Gd@C
82
(OH)
22
functions as an inhibitor of breast cancer stem cell function via blocking TGF-β and HIF-1α signalling, while sparing normal tissue. 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-1α 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. 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@C 82 (OH) 22 , while essentially not toxic to normal mammary epithelial cells, possesses intrinsic inhibitory activity against triple-negative breast cancer cells. Gd@C 82 (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@C 82 (OH) 22 mediates these effects by blocking TGF-β signalling. Moreover, under hypoxic conditions found in the tumour microenvironment, cellular uptake of Gd@C 82 (OH) 22 is facilitated where it functions as a bi-potent inhibitor of HIF-1α 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. |
ArticleNumber | 5988 |
Author | Gao, Xingfa Zhang, Weijie Dong, Jinquan Tang, Jinglong Lu, Xuefei Sun, Baoyun Li, Han Zhang, Huafeng Lobie, Peter E. Zhao, Yuliang Wang, Liming Liu, Suling Zhang, Xiao Liu, Ying Wicha, Max S. Zhu, Tao Wu, Qingfa Zhao, Feng Chen, Chunying Qian, Pengxu Chen, Zhiyun Bai, Ru |
Author_xml | – sequence: 1 givenname: Ying surname: Liu fullname: Liu, Ying organization: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China and Institute of High Energy Physics, Chinese Academy of Sciences (CAS) – sequence: 2 givenname: Chunying surname: Chen fullname: Chen, Chunying organization: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China and Institute of High Energy Physics, Chinese Academy of Sciences (CAS) – sequence: 3 givenname: Pengxu surname: Qian fullname: Qian, Pengxu organization: Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China – sequence: 4 givenname: Xuefei surname: Lu fullname: Lu, Xuefei organization: Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China – sequence: 5 givenname: Baoyun surname: Sun fullname: Sun, Baoyun organization: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China and Institute of High Energy Physics, Chinese Academy of Sciences (CAS) – sequence: 6 givenname: Xiao surname: Zhang fullname: Zhang, Xiao organization: Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China – sequence: 7 givenname: Liming surname: Wang fullname: Wang, Liming organization: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China and Institute of High Energy Physics, Chinese Academy of Sciences (CAS) – sequence: 8 givenname: Xingfa surname: Gao fullname: Gao, Xingfa organization: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China and Institute of High Energy Physics, Chinese Academy of Sciences (CAS) – sequence: 9 givenname: Han surname: Li fullname: Li, Han organization: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China and Institute of High Energy Physics, Chinese Academy of Sciences (CAS) – sequence: 10 givenname: Zhiyun surname: Chen fullname: Chen, Zhiyun organization: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China and Institute of High Energy Physics, Chinese Academy of Sciences (CAS) – sequence: 11 givenname: Jinglong surname: Tang fullname: Tang, Jinglong organization: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China and Institute of High Energy Physics, Chinese Academy of Sciences (CAS) – sequence: 12 givenname: Weijie surname: Zhang fullname: Zhang, Weijie organization: Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China – sequence: 13 givenname: Jinquan surname: Dong fullname: Dong, Jinquan organization: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China and Institute of High Energy Physics, Chinese Academy of Sciences (CAS) – sequence: 14 givenname: Ru surname: Bai fullname: Bai, Ru organization: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China and Institute of High Energy Physics, Chinese Academy of Sciences (CAS) – sequence: 15 givenname: Peter E. surname: Lobie fullname: Lobie, Peter E. organization: Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Cancer Science Institute of Singapore and Department of Pharmacology, National University of Singapore – sequence: 16 givenname: Qingfa surname: Wu fullname: Wu, Qingfa organization: Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China – sequence: 17 givenname: Suling surname: Liu fullname: Liu, Suling organization: Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China – sequence: 18 givenname: Huafeng surname: Zhang fullname: Zhang, Huafeng organization: Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China – sequence: 19 givenname: Feng surname: Zhao fullname: Zhao, Feng organization: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China and Institute of High Energy Physics, Chinese Academy of Sciences (CAS) – sequence: 20 givenname: Max S. surname: Wicha fullname: Wicha, Max S. organization: Department of Internal Medicine, Comprehensive Cancer Center, University of Michigan – sequence: 21 givenname: Tao surname: Zhu fullname: Zhu, Tao email: zhut@ustc.edu.cn organization: Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China – sequence: 22 givenname: Yuliang surname: Zhao fullname: Zhao, Yuliang email: zhaoyuliang@ihep.ac.cn organization: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China and Institute of High Energy Physics, Chinese Academy of Sciences (CAS) |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/25612916$$D View this record in MEDLINE/PubMed |
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Snippet | The contemporary use of nanomedicines for cancer treatment has been largely limited to serving as carriers for existing therapeutic agents. Here, we provide... Abstract The contemporary use of nanomedicines for cancer treatment has been largely limited to serving as carriers for existing therapeutic agents. Here, we... |
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Title | Gd-metallofullerenol nanomaterial as non-toxic breast cancer stem cell-specific inhibitor |
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