This study focused on developing a dual-targeted nanodrug-delivery system functionalized with aptamers (APs) and transferrin (Tf) and co-loaded with daunorubicin (Drn) and luteolin (Lut) for leukemia therapy.AP- and Tf-containing oligonucleotide ligands were individually synthesized. Nanoparticles loaded with Drn and decorated with APs (AP-Drn NPs) and Lut-loaded Tf-functionalized NPs (Tf-Lut NPs) were prepared via self-assembly. These were then combined to form a dual-ligand, dual-drug nanodrug system (AP/Tf-Drn/Lut NPs). The therapeutic efficacy of this system was assessed in vitro using leukemia cell lines and in vivo using a cell-bearing mouse model, compared with single-ligand, single-drug, and free-drug formulations.The AP/Tf-Drn/Lut NPs were spherical, with an average size of 187.3 ± 5.3 nm, and achieved a drug-loading efficiency of approximately 85%. In vitro, the dual-ligand NPs demonstrated significantly higher cytotoxicity than single-ligand counterparts. NPs co-loaded with both drugs exhibited enhanced tumor-cell inhibition relative to single-drug NPs, indicating a synergistic effect. In vivo, AP/Tf-Drn/Lut NPs showed the most potent antileukemic activity with no detectable toxicity.AP/Tf-Drn/Lut NPs represent a promising targeted nanodrug-delivery platform for leukemia therapy, benefiting from the synergistic action of dual drugs, though challenges remain regarding stability during large-scale production and clinical translation.
