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Electromagnetic Field-Programmed Magnetic Vortex Nanodelivery System for Efficacious Cancer Therapy
Advanced Science ( IF 15.1 ) Pub Date : 2021-07-18 , DOI: 10.1002/advs.202100950
Xiaoli Liu 1, 2 , Yifan Zhang 3 , Yu Guo 4 , Wangbo Jiao 3 , Xiao Gao 1 , Wee Siang Vincent Lee 5 , Yanyun Wang 3 , Xia Deng 6 , Yuan He 3 , Ju Jiao 7 , Ce Zhang 8 , Guoqing Hu 4 , Xing-Jie Liang 2, 9 , Haiming Fan 1, 3
Affiliation  

Effective delivery of anticancer drugs into the nucleus for pharmacological action is impeded by a series of intratumoral transport barriers. Despite the significant potential of magnetic nanovehicles in electromagnetic field (EF)-activated drug delivery, modularizing a tandem magnetoresponsive activity in a one-nanoparticle system to meet different requirements at both tissue and cellular levels remain highly challenging. Herein, a strategy is described by employing sequential EF frequencies in inducing a succession of magnetoresponses in the magnetic nanovehicles that aims to realize cascaded tissue penetration and nuclear accumulation. This nanovehicle features ferrimagnetic vortex-domain iron oxide nanorings coated with a thermo-responsive polyethylenimine copolymer (PI/FVIOs). It is shown that the programmed cascading of low frequency (Lf)-EF-induced magnetophoresis and medium frequency (Mf)-EF-stimulated magneto-thermia can steer the Doxorubicin (DOX)-PI/FVIOs to the deep tissue and subsequently trigger intracellular burst release of DOX for successful nuclear entry. By programming the order of different EF frequencies, it is demonstrated that first-stage Lf-EF and subsequent Mf-EF operation enables DOX-PI/FVIOs to effectively deliver 86.2% drug into the nucleus in vivoThis nanodelivery system empowers potent antitumoral activity in various models of intractable tumors, including DOX-resistant MCF-7 breast cancer cells, triple-negative MDA-MB-231 breast cancer cells, and BxPC-3 pancreatic cancer cells with poor permeability.

中文翻译:

用于有效癌症治疗的电磁场编程磁涡纳米递送系统

一系列瘤内转运障碍阻碍了抗癌药物有效递送至细胞核内发挥药理作用。尽管磁性纳米载体在电磁场(EF)激活的药物输送中具有巨大潜力,但在单纳米颗粒系统中模块化串联磁响应活性以满足组织和细胞水平的不同要求仍然极具挑战性。在此,描述了一种策略,通过采用连续的 EF 频率在磁性纳米载体中诱导一系列磁响应,旨在实现级联的组织穿透和核积累。这种纳米车辆具有亚铁磁涡旋域氧化铁纳米环,涂有热响应聚乙烯亚胺共聚物(PI/FVIO)。结果表明,低频 (L f )-EF 诱导的磁泳和中频 (M f )-EF 刺激的磁热的程序级联可以将多柔比星 (DOX)-PI/FVIO 引导至深层组织,随后触发细胞内 DOX 的爆发释放,以成功进入细胞核。通过对不同EF频率的顺序进行编程,证明第一阶段L f -EF和随后的M f -EF操作使DOX-PI/FVIO能够在体内有效地将86.2%的药物递送到细胞核中。 该纳米递送系统在各种难治性肿瘤模型中具有有效的抗肿瘤活性,包括 DOX 耐药性 MCF-7 乳腺癌细胞、三阴性 MDA-MB-231 乳腺癌细胞和渗透性差的 BxPC-3 胰腺癌细胞。
更新日期:2021-09-22
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