The State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory of Biomaterials and Devices, School of Biological Sciences and Medical Engineering, Southeast University, Dingjiaqiao 87, Nanjing 210009, China.
Drum Tower Hospital Affiliated to Medical School of Nanjing University, Zhongshan Road 321, Nanjing 210008, China.
Cells. 2022 Jun 23;11(13):2007. doi: 10.3390/cells11132007.
Leukemia is a non-solid cancer which features the malignant proliferation of leukocytes. Excessive leukocytes of lesions in peripheral blood will infiltrate organs, resulting in intumescence and weakening treatment efficiency. In this study, we proposed a novel approach for targeted clearance of the leukocytes in the peripheral blood ex vivo, which employed magnetic nanochains to selectively destroy the leukocytes of the lesions. The nanochains were doxorubicin-loaded nanochains of FeO nanoparticles which were fabricated by the solvent exchange method combined with magnetic field-directed self-assembly. Firstly, the nanochains were added into the peripheral blood during extracorporeal circulation and subjected to a rotational magnetic field for actuation. The leukocytes of the lesion were then conjugated by the nanochains via folic acid (FA) targeting. Finally, the rotational magnetic field actuated the nanochains to release the drugs and effectively damage the cytomembrane of the leukocytes. This strategy was conceptually shown in vitro (K562 cell line) and the method's safety was evaluated in a rat model. The preliminary results demonstrate that the nanochains are biocompatible and suitable as drug carriers, showing direct lethal action to the leukemic cells combined with a rotational magnetic field. More importantly to note is that the nanochains can be effectively kept from entry into the body. We believe this extracorporeal circulation-based strategy by activating nanochains magnetically could serve as a potential method for leukemia treatment in the future.
白血病是非实体瘤，其特征是白细胞的恶性增殖。病变部位外周血中过多的白细胞会浸润器官，导致肿大，降低治疗效果。在本研究中，我们提出了一种新的体外靶向清除外周血白细胞的方法，该方法采用磁性纳米链选择性破坏病变部位的白细胞。纳米链是通过溶剂交换法结合磁场导向自组装制备的载有阿霉素的 FeO 纳米颗粒的纳米链。首先，在外周血体外循环过程中加入纳米链，并施加旋转磁场进行驱动。病变部位的白细胞通过叶酸（FA）靶向与纳米链结合。最后，旋转磁场驱动纳米链释放药物，有效破坏白细胞的细胞质。该策略在体外（K562 细胞系）进行了概念验证，并在大鼠模型中评估了该方法的安全性。初步结果表明，纳米链具有生物相容性，适合作为药物载体，与旋转磁场结合对白血病细胞具有直接致死作用。更值得注意的是，纳米链可以有效地阻止进入体内。我们相信，这种基于体外循环的通过磁场激活纳米链的策略可能成为未来白血病治疗的一种潜在方法。
