NRP-1 targeted and cargo-loaded exosomes facilitate simultaneous imaging and therapy of glioma in vitro and in vivo
NRP-1 targeted and cargo-loaded exosomes facilitate simultaneous imaging and therapy of glioma in vitro and in vivo
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DOI：
10.1016/j.biomaterials.2018.06.029
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发表时间：
2018-09-01
期刊：
影响因子：
14
通讯作者：
Tang, Qiusha
中科院分区：
文献类型：
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作者：
Jia, Gang;Han, Yong;Tang, Qiusha
目前，胶质瘤的治疗受到两个主要因素的限制：发病或复发时的及时检测，以及血脑屏障（BBB）对药物进入大脑并影响肿瘤生长的限制。然而，一种安全的可穿越血脑屏障的药物递送系统为胶质瘤的治疗带来了新的希望。外泌体具有很强的载物能力，并且能够穿越血脑屏障，还可被赋予靶向递送的能力。因此，外泌体有很大的希望成为一种靶向药物递送载体。在这项研究中，我们首先将超顺磁性氧化铁纳米粒子（SPIONs）和姜黄素（Cur）装载到外泌体中，然后通过点击化学将外泌体膜与神经纤毛蛋白 - 1靶向肽（RGERPPR，RGE）结合，以获得具有成像和治疗功能的靶向胶质瘤的外泌体。当将其应用于胶质瘤细胞和原位胶质瘤模型时，我们发现这些经过工程改造的外泌体能够顺利穿越血脑屏障，并在胶质瘤的靶向成像和治疗方面取得了良好的效果。此外，SPION介导的磁流热疗（MFH）和Cur介导的治疗也显示出强大的协同抗肿瘤效应。因此，在减少副作用的同时，对胶质瘤的诊断和治疗效果得到了显著提高。我们设计了一种新型的靶向胶质瘤的外泌体，它可以携带纳米材料和化学药物用于胶质瘤的同时诊断和治疗，从而为提高颅内肿瘤的诊断和治疗效果提供了一种潜在的方法。（C）2018爱思唯尔有限公司。保留所有权利。
Currently, glioma treatment is limited by two main factors: timely detection at onset or relapse and restriction of drugs by the blood-brain barrier (BBB) from entering the brain and influencing tumor growth. However, a safe BBB-traversing drug delivery system has brought new hope to glioma treatment. Exosomes have strong cargo-loading capacity and have the ability to cross the BBB. They can also be conferred with the ability for targeted delivery. Therefore, exosomes have great promise to be a targeted drug delivery vehicles. In this study, we firstly loaded superparamagnetic iron oxide nanoparticles (SPIONs) and curcumin (Cur) into exosomes and then conjugated the exosome membrane with neuropilin-1-targeted peptide (RGERPPR, RGE) by click chemistry to obtain glioma-targeting exosomes with imaging and therapeutic functions. When administered to glioma cells and orthotopic glioma models, we found that these engineered exosomes could cross the BBB smoothly and provided good results for targeted imaging and therapy of glioma. Furthermore, SPION-mediated magnetic flow hyperthermia (MFH) and Cur-mediated therapy also showed a potent synergistic antitumor effect. Therefore, the diagnostic and therapeutic effects on glioma were significantly improved, while reducing the side effects. We have designed a new type of glioma-targeting exosomes, which can carry nanomaterials and chemical agents for simultaneous diagnosis and treatment of glioma, thus providing a potential approach for improving the diagnosis and treatment effects of intracranial tumors. (C) 2018 Elsevier Ltd. All rights reserved.