Dual-Targeted Aptamer/Transferrin-Functionalized Nanoparticles for Synergistic Delivery of Daunorubicin and Luteolin in Leukemia Therapy

The objective of this investigation was to construct a binary nanodrug-delivery system functionalized with aptamers (APs) and transferrin (Tf), and co-loaded with daunorubicin (Drn) and luteolin (Lut) for leukemia therapy. Ligand molecules bearing oligonucleotide AP and Tf were individually designed and fabricated. AP-functionalized Drn-loaded nanoparticles (AP-Drn NPs) along with Tf-Lut NPs were generated through a self-assembly process. An AP- and Tf-co-functionalized, Drn- and Lut-co-loaded nanodrug-delivery system (AP/Tf-Drn/Lut NPs) was subsequently produced by the self-assembly of AP-Drn NPs with Tf-Lut NPs. The in vitro and in vivo performance characteristics of this system were examined in a leukemia cell line and a tumor-bearing mouse model, and contrasted with single-ligand–functionalized, single-drug–loaded, and free-drug preparations. AP/Tf-Drn/Lut NPs possessed a spherical morphology and a nanoscale diameter (187.3 ± 5.3 nm), with roughly 85% drug-encapsulation efficiency. In vitro, the cytotoxic potency of AP/Tf-Drn/Lut NPs substantially exceeded that of single ligand–functionalized variants. Dual drug–loaded AP/Tf-Drn/Lut NPs demonstrated superior tumor-cell suppression compared with single–drug–loaded counterparts, reflecting a cooperative interaction between the two therapeutic agents. In vivo, AP/Tf-Drn/Lut NPs demonstrated the highest antileukemic efficacy with no detectable toxicity. The current investigation revealed that AP/Tf-Drn/Lut NPs represent a viable drug-delivery platform for the targeted management of leukemia, owing to the cooperative pharmacological interplay of the two agents within this construct. Constraints associated with this platform encompass stability issues during scaled-up manufacture and the translational pathway from preclinical research to clinical practice.