目前，高剂量的阿糖胞苷（Ara-C）联合化疗常用于急性髓性白血病（AML）治疗，但由于缺乏靶向选择性，阿糖胞苷基于化疗的严重不良反应和白血病细胞的抑制效果差，限制了其临床治疗效果。为提高阿糖胞苷在AML中的治疗效果，我们证实了转铁蛋白受体1（TFRC）在AML细胞中的表达是恒定的，并通过将自由的阿糖胞苷封装到自组装的重性铁蛋白链（HFn，TFRC的配体）纳米笼中生成了Ara-C@HFn。临床相关数据分析表明，AML细胞中TFRC的高表达水平不会在治疗阿糖胞苷后显著降低。Ara-C@HFn可以被白血病细胞高效内吞，并在体外显示出更强的细胞毒性效果，在AML小鼠中更有效地减轻了白血病的负担，比自由的Ara-C更优。Ara-C@HFn处理对小鼠的内脏器官没有急性毒性。此外，临床相关数据分析还表明，有几种药物（如他脯醇和ABT199）不会导致AML细胞中TFRC表达下调。以上结果表明，TFRC可以用作AML细胞药物靶向传递的恒定和有效的靶点。因此，Ara-C@HFn处理可以通过将Ara-C特异性地输送到AML细胞，成为AML治疗的安全和高效策略。此外，HFn纳米笼对于改善不会导致AML细胞中TFRC表达下调的其他与AML相关的治疗药物的抗肿瘤效果具有前景。© 2023. 作者。

Currently, high doses of cytarabine arabinoside (Ara-C)-based combined chemotherapy are commonly used in acute myeloid leukemia (AML) therapy, but severe adverse effects and poor suppression effects in leukemia cells limit the clinical therapeutic efficiency of Ara-C-based chemotherapy due to a lack of targeting selectivity. To improve the therapeutic effect of Ara-C in AML, here, since we confirmed that transferrin receptor 1 (TFRC) expression in AML cells was constant, we generated Ara-C@HFn by encapsulating free Ara-C into self-assembled heavy ferritin chain (HFn, the ligand of TFRC) nanocages.The analysis of clinically relevant data suggested that the high expression levels of TFRC from AML cells would not decrease significantly after treatment with Ara-C. Ara-C@HFn can be efficiently internalized by leukemia cells, showing stronger cytotoxic effects in vitro and reducing the burden of leukemia in AML mice more effectively in vivo than free Ara-C. Ara-C@HFn treatment showed no acute toxicity in visceral organs of mice. Moreover, the analysis of clinically relevant data also suggested that there are several drugs (such as tamibarotene and ABT199) that would not cause significant expression down-regulation of TFRC in AML cells (after treatment).The above results suggested that TFRC can be used as a constant and effective target for drug targeting delivery of AML cells. Thus Ara-C@HFn treatment can become a safe and efficient strategy for AML therapy by specifically delivering Ara-C to AML cells. Besides, the HFn nanocages are promising for improving antineoplastic effect of other AML-related therapy drugs that do not cause downregulated expression of TFRC in AML cells.© 2023. The Author(s).