Efficient therapy of glioblastoma remains a big clinical challenge due to the existence of a blood–brain barrier (BBB) that prevents the delivery of anti-cancer drugs to the brain. In this study, a HER2 antibody-conjugated selenium nanoparticle platform was rationally designed and synthesised and was found to be capable of overcoming the BBB efficiently and delivering anti-cancer cargoes precisely to brain tissues. The BBB-overcoming efficacy of the nanosystem (HER2@NPs) was evaluated using in vitro cell co-culture model and in vivo mouse model. The results demonstrated that HER2 functionalization effectively enhanced BBB permeability of the NPs, which could significantly inhibit the growth of U251 glioblastoma tumor spheroids. Examination of the action mechanisms revealed that HER2@NPs entered the cancer cells through receptor-mediated endocytosis and then triggered DNA damage-mediated p53 signalling pathways. Moreover, by using superparamagnetic iron oxide nanoparticles (SPIONs) as a probe in a clinically used magnetic resonance imaging (MRI) system, we found that HER2@NPs effectively deliver SPIONs into the brain. Taken together, this study provides a cancer-targeting nanosystem for the delivery of anti-cancer drugs and MRI contrast agents overcoming the BBB to enable a precise future theranosis of malignant glioma in humans.

中文翻译：

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通过靶向HER2的纳米系统克服血脑屏障，抑制胶质母细胞瘤细胞迁移，侵袭和肿瘤生长†

胶质母细胞瘤的有效治疗仍然是一项巨大的临床挑战，因为存在血脑屏障（BBB），阻止了抗癌药物向大脑的传递。在这项研究中，合理设计和合成了HER2抗体偶联的硒纳米颗粒平台，发现该平台能够有效克服BBB并将抗癌药物精确地递送至脑组织。使用体外细胞共培养模型和体内评估了纳米系统（HER2 @ NPs）克服BBB的功效鼠标模型。结果表明，HER2功能化可有效增强NPs的BBB渗透性，从而可显着抑制U251胶质母细胞瘤肿瘤球体的生长。作用机制的研究表明，HER2 @ NPs通过受体介导的内吞作用进入癌细胞，然后触发DNA损伤介导的p53信号通路。此外，通过在临床使用的磁共振成像（MRI）系统中使用超顺磁性氧化铁纳米粒子（SPIONs）作为探针，我们发现HER2 @ NPs有效地将SPIONs传递到大脑中。两者合计，这项研究提供了一种靶向癌症的纳米系统，可用于克服BBB的抗癌药物和MRI造影剂的交付，从而使人类恶性神经胶质瘤的未来精确治疗成为可能。