School of Medicine, Chongqing University, Chongqing, 400044, China; Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, 400044, China.
Key Laboratory of Human-Machine-Intelligence Synergic Systems, Research Center for Neural Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China.
Biomaterials. 2021 Jun;273:120784. doi: 10.1016/j.biomaterials.2021.120784. Epub 2021 Mar 31.
Clinical treatment of malignant glioma remains a major challenge due to high infiltrative growth and chemotherapeutic resistance of tumors and the presence of the blood brain barrier (BBB). Advanced nanoplatforms that can efficiently cross the BBB and target to brain tumor are urgently needed. Encouraged by the intrinsic inflammatory chemotaxis and excellent BBB-crossing capability of neutrophils, a bioinspired neutrophil-exosomes (NEs-Exos) system for delivering loaded doxorubicin (DOX) drug for glioma treatment is proposed and systematically investigated. In vivo zebrafish and C6-Luc glioma-bearing mice models show that NEs-Exos carrying the drug rapidly penetrate the BBB and migrate into the brain. Additionally, a transwell BBB model and mouse brain inflammatory study show that NEs-Exos can respond chemotactically to inflammatory stimuli and target infiltrating tumor cells in inflamed brain tumors. Moreover, intravenous injection of NEs-Exos/DOX efficiently suppress tumor growth and prolong survival time in a glioma mouse model. On the basis of these results, NEs-Exos are confirmed to have neutrophil-like chemotactic function and BBB penetration. This novel NEs-Exos/DOX delivery platform represents a promising chemotherapeutic approach for clinical treatment of glioma and other solid tumor or brain diseases.
由于肿瘤的高浸润性生长和化疗耐药性以及血脑屏障（BBB）的存在，恶性神经胶质瘤的临床治疗仍然是一个主要挑战。迫切需要能够有效穿透血脑屏障并靶向脑肿瘤的先进纳米平台。受中性粒细胞固有炎症趋化性和出色的 BBB 穿透能力的启发，提出并系统研究了一种仿生中性粒细胞外泌体（NEs-Exos）系统，用于递送负载多柔比星（DOX）药物治疗神经胶质瘤。体内斑马鱼和 C6-Luc 神经胶质瘤荷瘤小鼠模型表明，携带药物的 NEs-Exos 可迅速穿透血脑屏障并迁移到大脑中。此外，Transwell BBB 模型和小鼠脑炎症研究表明，NEs-Exos 可以对炎症刺激产生趋化反应，并靶向炎症性脑肿瘤中的浸润性肿瘤细胞。此外，静脉注射 NEs-Exos/DOX 可有效抑制神经胶质瘤小鼠模型中的肿瘤生长并延长存活时间。基于这些结果，证实 NEs-Exos 具有类似中性粒细胞的趋化功能和穿透 BBB 的能力。这种新型 NEs-Exos/DOX 递药平台代表了一种有前途的治疗神经胶质瘤和其他实体瘤或脑部疾病的化疗方法。
