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

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...

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Detalles Bibliográficos
Autores principales: Xiang, Dongxi, Shigdar, Sarah, Bean, Andrew G, Bruce, Matthew, Yang, Wenrong, Mathesh, Motilal, Wang, Tao, Yin, Wang, Tran, Phuong Ha-Lien, Al Shamaileh, Hadi, Barrero, Roberto A, Zhang, Pei-Zhuo, Li, Yong, Kong, Lingxue, Liu, Ke, Zhou, Shu-Feng, Hou, Yingchun, He, Aina, Duan, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2017
Materias:
Research Paper
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5694998/
https://www.ncbi.nlm.nih.gov/pubmed/29158811
http://dx.doi.org/10.7150/thno.20168
Descripción
Sumario: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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