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

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

146 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

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
Physics and Astronomy(all)

Access to Document

10.1038/ncomms6988

Cite this

@article{c2179f6587554e5bbcbc78b1c6d47f05,

title = "Gd-metallofullerenol nanomaterial as non-toxic breast cancer stem cell-specific inhibitor",

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",

note = "Funding Information: This work was financially supported by the MOST (2012CB934000, 2011CB933400), the NSFC (21320102003, 21001034, 81272925, 11425520), International Science & Technology Cooperation Program of MOST (2013DFG32340), National Major Scientific Instruments Development Project (2011YQ03013406), Chinese Academy of Sciences (XDA01040410, XDA09090302), the Cancer Science Institute of Singapore through grants from the National Research Foundation and the Ministry of Education and National Medical Research Council of Singapore (R-713-000-163-511). Publisher Copyright: {\textcopyright} 2015 Macmillan Publishers Limited. All rights reserved.",

year = "2015",

month = feb,

doi = "10.1038/ncomms6988",

language = "English (US)",

volume = "6",

journal = "Nat Commun",

issn = "2041-1723",

publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Gd-metallofullerenol nanomaterial as non-toxic breast cancer stem cell-specific inhibitor

AU - Liu, Ying

AU - Chen, Chunying

AU - Qian, Pengxu

AU - Lu, Xuefei

AU - Sun, Baoyun

AU - Zhang, Xiao

AU - Wang, Liming

AU - Gao, Xingfa

AU - Li, Han

AU - Chen, Zhiyun

AU - Tang, Jinglong

AU - Zhang, Weijie

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

N1 - Funding Information: This work was financially supported by the MOST (2012CB934000, 2011CB933400), the NSFC (21320102003, 21001034, 81272925, 11425520), International Science & Technology Cooperation Program of MOST (2013DFG32340), National Major Scientific Instruments Development Project (2011YQ03013406), Chinese Academy of Sciences (XDA01040410, XDA09090302), the Cancer Science Institute of Singapore through grants from the National Research Foundation and the Ministry of Education and National Medical Research Council of Singapore (R-713-000-163-511). Publisher Copyright: © 2015 Macmillan Publishers Limited. All rights reserved.

PY - 2015/2

Y1 - 2015/2

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.

UR - http://www.scopus.com/inward/record.url?scp=84923166604&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84923166604&partnerID=8YFLogxK

U2 - 10.1038/ncomms6988

DO - 10.1038/ncomms6988

M3 - Article

C2 - 25612916

AN - SCOPUS:84923166604

VL - 6

JO - Nat Commun

JF - Nat Commun

SN - 2041-1723

M1 - 5988

ER -

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

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this