Aptamer-targeted hybrid nanoparticles based on human exosomes and LXR agonist-loaded liposomes for enhanced anti-AML therapy.

Despite advances in acute myeloid leukemia (AML) research, the treatment of AML is still inadequate, with relapse rates exceeding 50% in high-risk patients. There is an urgent need for the development of novel and synergistic therapies. In this study, we devised a Liver X Receptor (LXR) agonist, T0901317, employing the CD123 aptamer as a targeting element and exosome-liposome hybrid nanoparticles as delivery vehicles: aptamer mediated exosome-liposome hybridized nanoparticles@T0901317 (A-ELHN@T0901317). The A-ELHN@T0901317 was successfully synthesized with a uniform size of 162.0 ± 2.082 nm (PDI: 0.2368 ± 0.01845), ideal encapsulation efficiency (83.17 ± 2.881% for T0901317). In vitro, A-ELHN@T0901317 exhibited higher cellular uptake in CD123+ AML cells (molm-13) compared to non-targeted nanoparticles and a ∼50% reduction in cell proliferation relative to the control (p < 0.01). It induced G0/G1 cell cycle arrest and increased apoptosis via LXR-mediated cholesterol metabolism regulation (up-regulation of ARG1, ABCA1, ABCG1, LXRβ, FASN, ACACA, SREBF1, CDKN1A, and SCD genes). In vivo, A-ELHN@T0901317 group exhibited a substantially smaller fold increase in tumor fluorescence (21.38 ± 5.428-fold) than the control group (61.57 ± 17.73-fold, p < 0.0001), while significantly reduced damage to normal organs. Our findings suggest that A-ELHN@T0901317 represents a novel delivery method for the treatment of AML and highlights a promising direction for tumor-targeted therapy.