Abstract
The standard treatment for most acute myeloid leukemia (AML) is chemotherapy, which is often associated with severe adverse effects. One strategy to reduce the adverse effects is targeted therapy that can selectively deliver anticancer drugs to tumor cells. Immature laminin receptor protein (OFA/iLRP) is a potential target for AML treatment, because it is over-expressed on the surface of AML cells but under-expressed in normal tissue. In this study, we developed the first aptamer for OFA/iLRP and explored its potential as a targeting ligand for delivery of doxorubicin (Dox) to AML cells in vitro. The selected aptamer (AB3) was a 59-base DNA oligonucleotides. It bound to OFA/iLRP structure with a K(d) of 101 nM and had minimal cross-reactivity to albumin, trypsin, or ovalbumin. Moreover, AB3 could bind to OFA/iLRP-positive AML cells but not the OFA/iLRP-negative control cells. An aptamer-doxorubicin (Apt-Dox) complex was formed by intercalating doxorubicin into the DNA structure of AB3. Apt-Dox selectively delivered Dox to OFA/iLRP-positive AML cells but notably decreased the drug intake by OFA/iLRP-negative control cells. In addition, cytotoxicity study revealed that Apt-Dox efficaciously destroyed the OFA/iLRP-positive AML cells, but significantly reduced the damage to control cells. The results indicate that the OFA/iLRP aptamer AB3 may have application potential in targeted therapy against AML.