Co-Delivery of Daunorubicin and Homoharringtonine in Folic Acid Modified-Liposomes for Enhancing Therapeutic Effect on Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) remains a threatening disease due to severe complications, drug resistance, and high recurrence rates. Many drug combinations have demonstrated enhanced therapeutic effects in clinical practice. However, it requires complicated dosing regimens and is accompanied by increased toxicity. This study explored the combined effect of two therapeutic agents, daunorubicin (DNR) and homoharringtonine (HHT) in cell viability, apoptosis, and cell cycle in vitro and verified their synergistic effect. We encapsulated the two drugs into liposomes to construct a folic acid-modified co-delivery system (FA-DH-LP) to achieve an effective and safe therapeutic strategy. The FA-DH-LP was prepared by film hydration method. The resultant FA-DH-LP was homogeneously spherical and showed good blood compatibility with high encapsulation efficiency for DNR and HHT. The FA-DH-LP exhibited higher cellular uptake in HL60 and K562 cells and enhanced cytotoxicity than DNR/HHT co-delivery liposomes without folic acid modification (DH-LP) in vitro. In the HL60 subcutaneous xenotransplantation model, FA-DH-LP showed improved tumor targeting ability, anti-leukemia activity and safety profile superior to free combinational drugs and DH-LP after 18-day treatment. The results demonstrated that FA-DH-LP might present a promising delivery strategy to improve the efficacy of the two combinational chemotherapeutics while reducing toxicity.