xiang-transformingdoxorubicin-2017.pdf (2.14 MB)
Transforming doxorubicin into a cancer stem cell killer via EpCAM aptamer-mediated delivery
journal contribution
posted on 2017-01-01, 00:00 authored by Dongxi Xiang, Sarah ShigdarSarah Shigdar, A G Bean, M Bruce, Wenrong YangWenrong Yang, M Mathesh, Tao Wang, Wang Yin, Phuong TranPhuong Tran, H A Shamaileh, R A Barrero, P Z Zhang, Y Li, Lingxue KongLingxue Kong, K Liu, S F Zhou, Y Hou, A He, Wei DuanWei DuanChemotherapy-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.
History
Journal
TheranosticsVolume
7Issue
17Pagination
4071 - 4086Publisher
Ivyspring International PublisherLocation
Sydney, N.S.W.Publisher DOI
eISSN
1838-7640Language
engPublication classification
C Journal article; C1 Refereed article in a scholarly journalCopyright notice
2017, Ivyspring International PublisherUsage metrics
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