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.

由于严重的并发症、耐药性和高复发率，急性髓性白血病 (AML) 仍然是一种威胁性疾病。许多药物组合已在临床实践中显示出增强的治疗效果。然而，它需要复杂的给药方案并且伴随着增加的毒性。本研究探讨了两种治疗剂柔红霉素 (DNR) 和高三尖杉酯碱 (HHT) 在体外对细胞活力、细胞凋亡和细胞周期的联合作用并验证了它们的协同作用。我们将这两种药物封装到脂质体中，构建了叶酸修饰的共递送系统（FA-DH-LP），以实现有效且安全的治疗策略。FA-DH-LP采用薄膜水化法制备。所得 FA-DH-LP 呈均匀球形，显示出良好的血液相容性以及对 DNR 和 HHT 的高包封率。FA-DH-LP 在 HL60 和 K562 细胞中表现出更高的细胞摄取，并且在体外比没有叶酸修饰的 DNR/HHT 共递送脂质体 (DH-LP) 具有更高的细胞毒性. 在 HL60 皮下异种移植模型中，经过 18 天的治疗后，FA-DH-LP 显示出优于自由组合药物和 DH-LP 的更好的肿瘤靶向能力、抗白血病活性和安全性。结果表明，FA-DH-LP 可能提供一种有前途的递送策略，以提高两种联合化疗药物的疗效，同时降低毒性。