基于铁蛋白的砷靶向递送用于白血病的治疗

三价砷是治疗急性早幼粒细胞白血病患者的有效药物，但其离子性质导致几个主要限制，如白血病细胞中的低有效浓度和实质性的脱靶细胞毒性，这限制了其对其他类型的白血病的一般应用。在这里，基于我们的临床发现，来自不同白血病形式的患者的癌细胞具有稳定而强烈的CD71表达，我们设计了一种基于铁蛋白的As纳米药物，As@Fn，与白血病细胞结合具有非常高的亲和力，并有效地递送细胞毒性As第三转化为大量白血病细胞系和患者细胞。此外，As@Fn在各种细胞系衍生的异种移植模型以及患者来源的异种移植模型中发挥了很强的抗白血病作用，其中它始终优于金标准，显示出其作为多种白血病的精确治疗的潜力。

Arsenic(III) is an effective therapeutic agent for patients with acute promyelocytic leukemia (APL). However, its ionic nature imposes several major limitations, including low effective intracellular concentration in leukemia cells and substantial off-target cytotoxicity, which restrict its general application to other types of leukemia. Based on our clinical findings that cancer cells from patients with diverse leukemia subtypes exhibit stable and robust CD71 expression, we developed a ferritin-based arsenic nanomedicine, As@Fn, which binds to leukemia cells with extremely high affinity and efficiently delivers cytotoxic As(III) to a broad panel of leukemia cell lines and patient-derived cells. Furthermore, As@Fn exerts potent anti-leukemic effects across both various cell line-derived xenograft (CDX) models and patient-derived xenograft (PDX) models, where it consistently outperforms the gold standard, demonstrating its potential as a precision therapy for multiple leukemia subtypes.

搜集汇总

背景与挑战

背景概述

该数据集涉及一种基于铁蛋白的纳米药物As@Fn，旨在通过靶向递送三价砷来治疗白血病。它解决了砷治疗中低有效浓度和脱靶毒性的限制，在多种白血病模型（包括患者来源的异种移植模型）中表现出强抗白血病效果，并优于现有标准疗法，显示出作为精确治疗多种白血病类型的潜力。