Ferritin Nanocarrier Traverses the Blood Brain Barrier and Kills Glioma,ACS Nano

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Ferritin Nanocarrier Traverses the Blood Brain Barrier and Kills Glioma
ACS Nano ( IF 15.8 ) Pub Date : 2018-04-02 00:00:00 , DOI: 10.1021/acsnano.7b06969
Kelong Fan ₁ , Xiaohua Jia ₂ , Meng Zhou _{1,

3} , Kun Wang ₂ , João Conde ₄ , Jiuyang He ₁ , Jie Tian ₂ , Xiyun Yan _{1,

3}

Affiliation

Over the last decades, considerable efforts have been put into developing active nanocarrier systems that cross the blood brain barrier (BBB) to treat brain-related diseases such as glioma tumors. However, to date none have been approved for clinical usage. Here, we show that a human H-ferritin (HFn) nanocarrier both successfully crosses the BBB and kills glioma tumor cells. Its principle point of entry is the HFn receptor (transferrin receptor 1), which is overexpressed in both BBB endothelial cells (ECs) and glioma cells. Importantly, we found that HFn enters and exits the BBB via the endosome compartment. In contrast, upon specifically targeting and entering glioma cells, nearly all of the HFn accumulated in the lysosomal compartment, resulting in the killing of glioma tumor cells, with no HFn accumulation in the surrounding healthy brain tissue. Thus, HFn is an ideal nanocarrier for glioma therapy and possesses the potential to serve as a therapeutic approach against a broad range of central nervous system diseases.

中文翻译：

铁蛋白纳米载体穿越血脑屏障并杀死神经胶质瘤

在过去的几十年中，已经做出了巨大的努力来开发能穿过血脑屏障（BBB）来治疗脑相关疾病（例如神经胶质瘤）的活性纳米载体系统。但是，迄今为止，尚未批准将其用于临床。在这里，我们显示人类H-铁蛋白（HFn）纳米载体既可以成功穿越血脑屏障，又可以杀死神经胶质瘤肿瘤细胞。它的主要切入点是HFn受体（转铁蛋白受体1），它在BBB内皮细胞（ECs）和神经胶质瘤细胞中均过表达。重要的是，我们发现HFn通过内体隔室。相反，在特异性靶向并进入神经胶质瘤细胞后，几乎所有的HFn都在溶酶体区室中积聚，导致神经胶质瘤肿瘤细胞被杀死，周围健康的脑组织中没有HFn积聚。因此，HFn是神经胶质瘤治疗的理想纳米载体，具有潜力作为治疗多种中枢神经系统疾病的治疗方法。

更新日期：2018-04-02

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