Engineering Magnetosomes for Ferroptosis/Immunomodulation Synergism in Cancer
Engineering Magnetosomes for Ferroptosis/Immunomodulation Synergism in Cancer
复制标题
工程磁小体用于癌症铁死亡/免疫调节协同作用
DOI：
10.1021/acsnano.9b00892
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发表时间：
2019-05-01
期刊：
影响因子：
17.1
通讯作者：
Xie, Hai-Yan
中科院分区：
文献类型：
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作者：
Zhang, Fan;Li, Feng;Xie, Hai-Yan
由于传统的抗癌治疗不能显著改善肿瘤，因此迫切需要探索治疗方式。本文构建了一种仿生磁小体，以促进癌症中的铁凋亡/免疫调节协同作用。该磁小体由作为核心的Fe 304磁性纳米簇（NC）和作为外衣的预工程化白细胞膜组成，其中TGF-β 1抑制剂（Ti）可以负载在膜内部，并且PD-1抗体（Pa）可以锚定在膜表面上。在静脉注射后，膜伪装导致长循环，并且具有磁化和超顺磁性的NC核心能够在磁共振成像（MRI）引导下实现磁靶向。一旦在肿瘤内部，Pa和Ti协作以产生免疫原性微环境，其增加极化的MI巨噬细胞中的H2 O2的量，从而促进与从NC释放的Fe离子的反应。所产生的羟基自由基（*OH）随后诱导肿瘤细胞的致死性铁凋亡，而暴露的肿瘤抗原反过来又改善了微环境的免疫原性。因此，以这种循环方式的免疫调节和铁凋亡的协同作用导致具有很少异常的有效治疗效果，这支持工程化磁小体作为抗癌治疗的有前景的组合方式。
As traditional anticancer treatments fail to significantly improve the prognoses, exploration of therapeutic modalities is urgently needed. Herein, a biomimetic magnetosome is constructed to favor the ferroptosis/immunomodulation synergism in cancer. This magnetosome is composed of an Fe304 magnetic nanocluster (NC) as the core and pre-engineered leukocyte membranes as the cloak, wherein TGF-fl inhibitor (Ti) can be loaded inside the membrane and PD-1 antibody (Pa) can be anchored on the membrane surface. After intravenous injection, the membrane camouflage results in long circulation, and the NC core with magnetization and superparamagnetism enables magnetic targeting with magnetic resonance imaging (MRI) guidance. Once inside the tumor, Pa and Ti cooperate to create an immunogenic microenvironment, which increases the amount of H202 in polarized MI macrophages and thus promotes reaction with Fe ions released from NCs. The generated hydroxyl radicals (*OH) subsequently induce lethal ferroptosis to tumor cells, and the exposed tumor antigen, in turn, improves the microenvironment immunogenicity. The synergism of immunomodulation and ferroptosis in such a cyclical manner therefore leads to potent therapeutic effects with few abnormalities, which supports the engineered magnetosomes as a promising combination modality for anticancer therapy.