Medical School of Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, China.
Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School of Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, China.
Biomaterials. 2018 Sep;178:302-316. doi: 10.1016/j.biomaterials.2018.06.029. Epub 2018 Jun 21.
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.
目前，神经胶质瘤的治疗受到两个主要因素的限制：一是在发病或复发时的及时检测，二是血脑屏障（BBB）限制了药物进入大脑并影响肿瘤生长。然而，一种安全的 BBB 穿透性药物传递系统为神经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，能够穿透 BBB，并且还能够被赋予靶向递药的能力。因此，外泌体作为一种靶向药物传递载体具有很大的潜力。在本研究中，我们首先将超顺磁性氧化铁纳米粒子（SPIONs）和姜黄素（Cur）载入外泌体中，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）偶联，得到具有成像和治疗功能的神经胶质瘤靶向外泌体。当将这些工程化的外泌体给药于神经胶质瘤细胞和原位神经胶质瘤模型时，我们发现这些外泌体可以顺利穿透 BBB，并为神经胶质瘤的靶向成像和治疗提供了良好的效果。此外，SPION 介导的磁流热疗（MFH）和 Cur 介导的治疗也表现出很强的协同抗肿瘤作用。因此，显著提高了对神经胶质瘤的诊断和治疗效果，同时减少了副作用。我们设计了一种新型的神经胶质瘤靶向外泌体，它可以携带纳米材料和化学试剂，用于神经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。
