Theranostics 2017; 7(17):4071-4086. doi:10.7150/thno.20168

Research Paper

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

Dongxi Xiang1, Sarah Shigdar1, Andrew G Bean2, Matthew Bruce2, Wenrong Yang3, Motilal Mathesh3, Tao Wang1,4, Wang Yin1, Phuong Ha-Lien Tran1, Hadi Al Shamaileh1, Roberto A Barrero5, Pei-Zhuo Zhang6, Yong Li7, Lingxue Kong8, Ke Liu9, Shu-Feng Zhou10, Yingchun Hou11, Aina He12✉, Wei Duan1✉

1. School of Medicine and Centre for Molecular and Medical Research, Deakin University, 75 Pigdons Road, Waurn Ponds, Victoria 3216, Australia;
2. CSIRO Australian Animal Health Laboratory, Private Bag 24, Geelong, Victoria 3220, Australia;
3. Centre for Chemistry and Biotechnology, School of Life and Environmental Sciences, Faculty of Science, Engineering and Built Environment, Deakin University, Waurn Ponds, Victoria 3216, Australia;
4. School of Nursing, Zhengzhou University, 100 Kexue Ave, Zhengzhou, P. R. China, 450001;
5. Centre for Comparative Genomics, Murdoch University, 90 South Street, Murdoch, WA 6150, Australia;
6. Suzhou GenePharma, 199 Dongping Street, Suzhou 215123, P. R. China;
7. Cancer Care Centre, St George Hospital and St George and Suthland Clinical School, University of New South Wales (UNSW), High Street, Kensington, NSW 2052, Australia;
8. Deakin University, Australia, Institute for Frontier Materials, 75 Pigdons Road, Waurn Ponds, Victoria, 3216;
9. College of Life Sciences, Sichuan University, No.24 South Section 1, Yihuan Road, Chengdu 610041, P. R. China;
10. Department of Bioengineering and Biotechnology, College of Chemical Engineering, Huaqiao University, 668 Jimei Avenue, Xiamen, Fujian 361021, P. R. China;
11. Center for Qinba Region's Sustainable Development, Shaanxi Normal University, No.199, South Chang'an Road, Xi'an, Shaanxi 710062, P. R. China;
12. Department of Oncology, Affiliated Sixth People's Hospital, Shanghai Jiaotong University, No. 600, Yishan Road, Shanghai 200233, P. R. China.

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.

Keywords: doxorubicin, cancer stem cell killer

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How to cite this article:
Xiang D, Shigdar S, Bean AG, Bruce M, Yang W, Mathesh M, Wang T, Yin W, Tran PHL, Al Shamaileh H, Barrero RA, Zhang PZ, Li Y, Kong L, Liu K, Zhou SF, Hou Y, He A, Duan W. Transforming doxorubicin into a cancer stem cell killer via EpCAM aptamer-mediated delivery. Theranostics 2017; 7(17):4071-4086. doi:10.7150/thno.20168. Available from http://www.thno.org/v07p4071.htm