Targeted drug delivery to AML by OFA/iLRP aptamer guided DNA nanostructure.

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.