An aptamer-based drug delivery agent (CD133-apt-Dox) selectively and effectively kills liver cancer stem-like cells

Journal Publication ResearchOnline@JCU
Zhou, Gang;Da Won Bae, Sarah;Nguyen, Romario;Huo, Xiaoqi;Han, Shuanglin;Zhang, Zhiqiang;Hebbard, Lionel;Duan, Wei;Eslam, Mohammed;Liddle, Christopher;Yuen, Lawrence;Lam, Vincent;Qiao, Liang;George, Jacob
Abstract

Liver cancer has no effective therapies, hence a poor survival. Cancer stem-like cells not only contribute to cancer initiation and progression, but also to drug resistance, cancer metastasis, and eventually treatment failure. Hence, any approaches that can effectively kill cancer stem-like cells hold a great potential for cancer treatment. CD133 is a robust marker for liver cancer stem-like cells. We developed a specific aptamer against CD133 (CD133-apt), and then loaded this aptamer with an anticancer drug doxorubicin (CD133-apt-Dox). The efficacy of CD133-apt-Dox in targeting liver cancer stem-like cells and its overall effect in treating liver cancer were investigated using multiple in vitro and in vivo studies including in patients-derived liver cancer organoids. We have observed that CD133-apt could preferably delivered doxorubicin to CD133-expressing cells with efficient drug accumulation and retention. CD133-apt-Dox impaired the self-renewal capacity of liver cancer stem-like cells and attenuated their stem-ness phenotypes in vitro or in vivo. CD133-apt-Dox significantly inhibited the growth of liver cancer cells and patients-derived organoids and reduced the growth of xenograft tumours in nude mice inhibited the growth of DEN-induced liver cancer in immunocompetent mice. Hence, aptamer-mediated targeting of CD133 is a highly promising approach for liver cancer therapy.

Journal

Cancer Letters

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501

ISBN/ISSN

1872-7980

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Pages Count

9

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Publisher

Elsevier

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DOI

10.1016/j.canlet.2020.12.022