State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, P. R. China.
School of Chemical Engineering, University of Chinese Academy of Sciences, Beijing, P. R. China.
Nat Nanotechnol. 2021 Dec;16(12):1413-1423. doi: 10.1038/s41565-021-00980-7. Epub 2021 Oct 25.
Trivalent arsenic (As) is an effective agent for treating patients with acute promyelocytic leukaemia, but its ionic nature leads to several major limitations like low effective concentrations in leukaemia cells and substantial off-target cytotoxicity, which limits its general application to other types of leukaemia. Here, building from our clinical discovery that cancerous cells from patients with different leukaemia forms featured stable and strong expression of CD71, we designed a ferritin-based As nanomedicine, As@Fn, that bound to leukaemia cells with very high affinity, and efficiently delivered cytotoxic As into a large diversity of leukaemia cell lines and patient cells. Moreover, As@Fn exerted strong anti-leukaemia effects in diverse cell-line-derived xenograft models, as well as in a patient-derived xenograft model, in which it consistently outperformed the gold standard, showing its potential as a precision treatment for a variety of leukaemias.
三价砷（As）是治疗急性早幼粒细胞白血病患者的有效药物，但由于其离子性质，存在有效浓度低和非靶向细胞毒性大等局限性，限制了其在其他类型白血病中的广泛应用。在这里，基于我们的临床发现，不同白血病类型的癌细胞稳定且强烈表达 CD71，我们设计了一种基于铁蛋白的砷纳米药物 As@Fn，它与白血病细胞具有非常高的亲和力，并能有效地将细胞毒性的 As 递送到多种白血病细胞系和患者细胞中。此外，As@Fn 在多种细胞系衍生的异种移植模型以及患者衍生的异种移植模型中表现出强烈的抗白血病作用，其疗效始终优于金标准药物，表明其有望成为各种白血病的精准治疗药物。
