ACUTE myeloid leukaemia (AML) remains a significant therapeutic challenge due to poor clinical outcomes and the considerable toxicity associated with conventional chemotherapy. A recent preclinical study has highlighted a novel aptamer-based targeted drug delivery system that enhances doxorubicin efficacy while reducing off-target cytotoxicity, offering a potential new avenue for AML treatment.
Development of a DNA Aptamer Nanostructure
The study focused on targeting the immature laminin receptor protein (OFA/iLRP), which is highly expressed on AML cells and represents a promising therapeutic target. Researchers optimised an existing aptamer, AB3, into a shortened functional variant called AB3-2. To further improve targeting capabilities, two AB3-2 aptamers were linked using complementary sticky ends to create a DNA nanostructure termed Apt-Couple, which measures approximately 11.7 nm. This nanostructure demonstrated selective binding to OFA/iLRP-positive AML cells, including the HL-60 cell line. By intercalating doxorubicin into the DNA framework, researchers generated Apt-Couple-Dox, capable of carrying around 18 molecules of the chemotherapeutic agent, enabling a concentrated delivery to malignant cells.
Efficacy and Safety Demonstrated In Vitro and In Vivo
In vitro studies revealed that Apt-Couple-Dox efficiently eradicated OFA/iLRP-positive AML cells while sparing control cells, indicating enhanced selectivity and reduced potential for collateral damage. In HL-60 tumour-bearing mice, treatment with Apt-Couple-Dox significantly improved anti-malignancy outcomes compared with free doxorubicin, and notably prolonged survival. Importantly, the targeted therapy did not increase systemic toxicity, suggesting a safer therapeutic profile than conventional chemotherapy regimens.
Clinical Potential for Targeted AML Therapy
These findings indicate that the OFA/iLRP aptamer AB3-2 can serve as an effective homing ligand for AML cells, and that Apt-Couple-Dox offers substantial promise in targeted chemotherapy strategies. By concentrating cytotoxic agents on malignant cells while sparing healthy tissues, this delivery system has the potential to reduce adverse effects, improve patient quality of life, and enhance overall treatment outcomes. Future studies may explore clinical translation and optimisation of this approach for patients with AML, addressing a long-standing challenge in oncology.
Reference
An Y et al. Targeted drug delivery to AML by OFA/iLRP aptamer guided DNA nanostructure. Scientific Reports. 2026;DOI:https://doi.org/10.1038/s41598-025-34487-1.
