Transforming doxorubicin into a cancer stem cell killer via EpCAM aptamer-mediated delivery

D. Xiang; S. Shigdar; A.G Bean; M. Bruce; W. Yang; M. Mathesh; T. Wang; W. Yin; P.H-L. Tran; H.A. Shamaileh; R.A. Barrero; P-Z Zhang; Y. Li; L. Kong; K. Liu; S-F Zhou; Y. Hou; A. He; W. Duan

doi:10.7150/thno.20168

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Transforming doxorubicin into a cancer stem cell killer via EpCAM aptamer-mediated delivery

Journal article

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Peer reviewed

Transforming doxorubicin into a cancer stem cell killer via EpCAM aptamer-mediated delivery

D. Xiang, S. Shigdar, A.G Bean, M. Bruce, W. Yang, M. Mathesh, T. Wang, W. Yin, P.H-L. Tran, H.A. Shamaileh, …

Theranostics, Vol.7(17), pp.4071-4086

2017

DOI: https://doi.org/10.7150/thno.20168

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Abstract

Chemotherapy-resistant cancer stem cells (CSCs) are a major obstacle to the effective treatment of many forms of cancer. To overcome CSC chemo-resistance, we developed a novel system by conjugating a CSC-targeting EpCAM aptamer with doxorubicin (Apt-DOX) to eliminate CSCs. Incubation of Apt-DOX with colorectal cancer cells resulted in high concentration and prolonged retention of DOX in the nuclei. Treatment of tumour-bearing xenograft mice with Apt-DOX resulted in at least 3-fold more inhibition of tumour growth and longer survival as well as a 30-fold lower frequency of CSC and a prolonged longer tumourigenic latency compared with those receiving the same dose of free DOX. Our data demonstrate that a CSC-targeting aptamer is able to transform a conventional chemotherapeutic agent into a CSC-killer to overcome drug resistance in solid tumours.

Details

Title: Transforming doxorubicin into a cancer stem cell killer via EpCAM aptamer-mediated delivery
Authors/Creators: D. Xiang (Author/Creator) - Deakin University
S. Shigdar (Author/Creator) - Deakin University
A.G Bean (Author/Creator) - Australian Centre for Disease Preparedness
M. Bruce (Author/Creator) - Australian Centre for Disease Preparedness
W. Yang (Author/Creator) - Deakin University
M. Mathesh (Author/Creator) - Deakin University
T. Wang (Author/Creator) - Zhengzhou University
W. Yin (Author/Creator) - Deakin University
P.H-L. Tran (Author/Creator) - Deakin University
H.A. Shamaileh (Author/Creator) - Deakin University
R.A. Barrero (Author/Creator) - Murdoch University
P-Z Zhang (Author/Creator) - Suzhou GenePharma, 199 Dongping Street, Suzhou 215123, P. R. China.
Y. Li (Author/Creator) - St George Hospital
L. Kong (Author/Creator) - Deakin University
K. Liu (Author/Creator) - Sichuan University
S-F Zhou (Author/Creator) - Jimei University
Y. Hou (Author/Creator) - Shaanxi Normal University
A. He (Author/Creator) - Shanghai Jiao Tong University
W. Duan (Author/Creator) - Deakin University
Publication Details: Theranostics, Vol.7(17), pp.4071-4086
Publisher: Ivyspring International Publisher
Identifiers: 991005543927607891
Copyright: © 2017 Ivyspring International Publisher.
Murdoch Affiliation: Centre for Comparative Genomics
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.108 Molecular & Cell Biology - Cancer & Development; 1.108.591 Cancer Stem Cells
Web Of Science research areas: Medicine, Research & Experimental
ESI research areas: Clinical Medicine