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 language | English |
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Pages (from-to) | 341-350 |
Number of pages | 10 |
Journal | Journal of Controlled Release |
Volume | 341 |
Early online date | 27 Nov 2021 |
DOIs | |
Publication status | Published - Jan 2022 |
Externally published | Yes |
Keywords
- Aptamer
- EpCAM
- HCC
- Organoids
- Dox
- cancer stem-like cells (CSCs)