Aptamer- vs Fab-Conjugated Liposomes: A Comparative Study in Targeting Acute Myeloid Leukemia Cells

Acute myeloid leukemia (AML) is a hematologic malignancy characterized by uncontrolled proliferation of abnormal myeloid cells with a generally poor prognosis despite advancements in chemotherapy and stem cell transplantation. To enhance therapeutic efficacy and minimize systemic toxicity, we designed liposomal nanoparticles functionalized with two distinct targeting ligands, a DNA aptamer or fragment-antigen-binding (Fab) antibody, targeting the surface marker transmembrane glycoprotein CD33 antigen (CD33) on AML cells. Aptamer- and Fab-conjugated liposomes (Apt-Lipm and Fab-Lipm, respectively) were prepared and tested for cellular uptake by CD33-positive AML cell lines. Comparative studies revealed that Fab-Lipm exhibited significantly superior binding affinity, targeting efficiency, and cellular uptake compared with Apt-Lipm. Furthermore, we demonstrated the intracellular distribution and endocytic pathways of Fab-Lipm during the cellular uptake. This comparative study of aptamer- and Fab-conjugated liposomes suggests that the Fab-conjugated liposomal system offers enhanced precision in targeting AML cells for the development of effective therapeutic strategies against hematologic malignancies.