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

Theranostics2017Vol. 7(17), pp. 4071–4086

Citations Over TimeTop 10% of 2017 papers

Dongxi Xiang, Sarah Shigdar, Andrew G. D. Bean, Matthew P. Bruce, Wenrong Yang, Motilal Mathesh, Tao Wang, Wang Yin, Phuong H.L. Tran, Hadi Al Shamaileh, Roberto A. Barrero, Pei-Zhuo Zhang, Yong Li, Lingxue Kong, Ke Liu, Shu-Feng Zhou, Yingchun Hou, Aina He, Wei Duan

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.

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