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

Gang Zhou, Sarah Da Won Bae, Romario Nguyen, Xiaoqi Huo, Shuanglin Han, Zhiqiang Zhang, Lionel Hebbard, Wei Duan, Mohammed Eslam, Christopher Liddle, Lawrence Yuen, Vincent Lam, Liang Qiao*, Jacob George

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

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.

Original languageEnglish
Pages (from-to)124-132
Number of pages9
JournalCancer Letters
Volume501
DOIs
Publication statusPublished - 31 Mar 2021
Externally publishedYes

Keywords

  • Aptamer
  • Cancer stem-like cells
  • CD133
  • Hepatocellular carcinoma (HCC)
  • Therapeutic targeting

Fingerprint

Dive into the research topics of 'An aptamer-based drug delivery agent (CD133-apt-Dox) selectively and effectively kills liver cancer stem-like cells'. Together they form a unique fingerprint.

Cite this