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

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 Wang^1,4, 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 He^12✉, Wei Duan^1✉

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.

✉ Corresponding author: Dr. Aina He, Department of Oncology, Affiliated Sixth People's Hospital, Shanghai Jiaotong University, No. 600, Yishan Road, Shanghai 200233, P. R. China. Tel: +86 21 2405 8430; E-mail: ai_na_hecom (A. He). Professor Wei Duan, School of Medicine, Deakin University, 75 Pigdons Road, Waurn Ponds, Victoria, 3217, Australia. Tel: +61 3 52271149; Fax: +61 3 52272945; E-mail: wduanedu.au (W. Duan) More

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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