Abstract
Acute myeloid leukemia (AML) has relatively poor clinical outcome. The primary treatment of AML is chemotherapy, which is often associated with severe adverse effects. Targeted drug delivery is a promising strategy to reduce the adverse effects of chemotherapy. Immature laminin receptor protein (OFA/iLRP) is a potential target for AML treatment. In this study, an OFA/iLRP aptamer (AB3) was optimized via sequence truncation to generate a shortened functional aptamer (AB3-2). Two AB3-2 aptamers were coupled together via sticky ends to form a DNA nanostructure (Apt-Couple) for targeted delivery of doxorubicin (Dox) to AML cells. Apt-Couple had an average size of 11.70 nm, and could selectively bind with OFA/iLRP-positive AML cells (HL-60). By intercalating Dox into the DNA structure of Apt-Couple, an Apt-Couple-Dox complex was formed and could carry approximately 18 Dox molecules. Moreover, Apt-Couple-Dox efficaciously destroyed OFA/iLRP-positive AML cells, but notably reduced the damage to control cells in vitro. Furthermore, in HL-60 bearing mice, Apt-Couple-Dox significantly improved the anti-malignancy efficacy compared with free Dox, and prolonged the survival of mice without raising systemic toxicity. These results indicate that the OFA/iLRP aptamer AB3-2 may serve as an AML-homing ligand, and that Apt-Couple-Dox has application potential in targeted therapy against AML.