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

Xiang, D., Shigdar, S., Bean, A.G, Bruce, M., Yang, W., Mathesh, M., Wang, T., Yin, W., Tran, P.H-L., Shamaileh, H.A., Barrero, R.A., Zhang, P-Z, Li, Y., Kong, L., Liu, K., Zhou, S-F, Hou, Y., He, A. and Duan, W. (2017) Transforming doxorubicin into a cancer stem cell killer via EpCAM aptamer-mediated delivery. Theranostics, 7 (17). pp. 4071-4086.

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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.

Item Type: Journal Article
Murdoch Affiliation(s): Centre for Comparative Genomics
Publisher: Ivyspring International Publisher
Copyright: © 2017 Ivyspring International Publisher.
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