As “roots
of cancer”, cancer stem cells (CSCs) are more resistant to traditional chemotherapy
and radiation than their non-CSC counterparts, and are responsible for the cancer
metastasis and recurrence. The existence of CSCs has opened a new avenue for
targeted cancer therapy. Aptamers, as chemical antibodies, are a novel means of
drug targeting and possess several significant advantages to antibodies in
anticancer applications. Using a CSC-targeted RNA aptamer, epithelial cell
adhesion molecule (EpCAM) we developed, we conjugated a traditional
chemotherapy agent doxorubicin (DOX) into this aptamer and evaluated its CSC-targeting
potential in a colon cancer model (derived from HT29 cells) in NOD/SCID mice. Following
four intravenous injection of various drugs, Apt-DOX but not free DOX or other
treatments remarkably inhibited tumour growth and extended the survival of mice-bearing
colon tumours (P < 0.001). The in vivo limiting dilution assay, a
gold standard for determining CSC functional properties, indicated that approximately
71.25 % of Apt-DOX mice failed to form new tumours. Remarkable reduction of FACS
CSC-characterised cells (EpCAM+CD24+CD44+ and ALDH+)
and 4.5-fold increase of apoptotic CSCs were also observed (P < 0.01 vs.
free DOX). Taken together, this strategy by conjugating a CSC-targeting aptamer
with an anticancer agent is able to seek CSCs, circumvent their drug resistance
and eliminate both CSCs and non-CSCs for inhibiting the tumour progression
eventually.