Aptamer-mediated doxorubicin delivery reduces HCC burden in 3D organoids model

Kevin Zhou, Xiaoqi Huo, Romario Nguyen, Sarah Da Won Bae, Shuanglin Han, Zhiqiang Zhang, Wei Duan, Lawrence Yuen, Vincent Lam, Jacob George, Liang Qiao

Research output: Contribution to journalArticlepeer-review

Abstract

Epithelial cell adhesion molecule (EpCAM) is a surface marker which is frequently overexpressed in hepato-cellular carcinoma (HCC) but minimally expressed on mature hepatocytes. We developed a specific aptamer against EpCAM (EpCAM-apt) and tested its potential as a drug delivery agent for HCC. The targeting ability of EpCAM-apt was confirmed in vitro and in vivo after which the complex was conjugated with doxorubicin (Dox) to form EpCAM-apt-Dox. The targeting efficacy of the drug-loaded complex against liver cancer stem-like cells (LCSCs) and therapeutic effects in HCC were evaluated. EpCAM-expressing (EpCAM(+)) HCC cells showed char-acteristics of stem like cells including greater proliferative capacity and tumour sphere formation. EpCAM-apt-Dox selectively delivered Dox to EpCAM(+) HCC cells with high drug retention and accumulation versus con-trol. EpCAM-apt-Dox reduced the self-renewal capacity and stem-like cell frequency in vitro. Elimination of cancer stem-like cells (CSCs) with EpCAM-apt-Dox significantly inhibited the growth of HCC cells and patient-derived HCC organoids but exerted minimal cytotoxicity to normal liver organoids. Moreover, EpCAM-apt-Dox suppressed the growth of xenograft tumours derived from HCC organoids in vivo and prolonged mouse survival without inducing adverse effects to major organs. Thus, aptamer-based drug delivery to the stem-like cell population is a promising strategy for HCC treatment.

Original languageEnglish
Pages (from-to)341-350
Number of pages10
JournalJournal of Controlled Release
Volume341
DOIs
Publication statusPublished - Jan 2022
Externally publishedYes

Keywords

  • Aptamer
  • EpCAM
  • HCC
  • Organoids
  • Dox
  • cancer stem-like cells (CSCs)

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