Deng Song, Nie Dekang, Huang Yue, Yang Yu, Liu Qianqian, Sun Zesheng, Jiang Qiaoji, Ling Yuejuan, Wen Ya, Qu Jiahua, Lin Jialiang, Wang Yi, Huang Rongqin, Shi Jinlong
Department of Neurosurgery, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, Jiangsu 226001, P.R. China.
Department of Neurosurgery, The Yancheng Clinical College of Xuzhou Medical University, The First People's Hospital of Yancheng, Yancheng, Jiangsu 224001, P.R. China.
Biomater Res. 2024 Dec 27;28:0123. doi: 10.34133/bmr.0123. eCollection 2024.
Glioblastoma multiforme (GBM) is among the most challenging malignant brain tumors, making the development of new treatment strategies highly necessary. Glioma stem cells (GSCs) markedly contribute to drug resistance, radiation resistance, and tumor recurrence in GBM. The therapeutic potential of nanomaterials targeting GSCs in GBM urgently needs to be explored. A magnetic-responsive biomimetic nanosystem (FDPM), coated with glioma stem cell membranes (CMs), was designed for the targeted eradication of GSCs as well as their associated tumor cells. Identified nanobodies were extensively characterized with various assays. The application tests on nanomaterials were conducted in vitro and in vivo. The tumor-suppressive effects of the nanosystem were evaluated in vitro and in vivo. FDPM can be artificially directed under magnetic guidance while inheriting various biological functions from CM. Upon intravenous injection, FDPM was drawn to the tumor site by magnetic attraction, where it could cross the blood-brain barrier aided by CM. Its homologous targeting ability originates from active proteins on CM, enabling it to specifically target GSCs and related tumor cells. The encapsulated doxorubicin (DOX) within the nanoparticle then destroyed these tumor cells. FDPM demonstrated excellent biocompatibility and tumor-targeting efficiency, effectively targeting malignant gliomas initiated by GSCs. FDPM significantly reduced tumor cells, inhibited tumor growth, and notably extended the survival of glioma-bearing nude mice. The findings position FDPM as a promising nanoplatform to target GSCs and related tumor cells for improving the therapeutic effect of glioma.
多形性胶质母细胞瘤（GBM）是最具挑战性的恶性脑肿瘤之一，因此开发新的治疗策略非常必要。胶质瘤干细胞（GSCs）在GBM的耐药性、抗辐射性和肿瘤复发中起显著作用。迫切需要探索针对GBM中GSCs的纳米材料的治疗潜力。设计了一种涂有胶质瘤干细胞膜（CMs）的磁响应仿生纳米系统（FDPM），用于靶向根除GSCs及其相关肿瘤细胞。通过各种检测方法对鉴定出的纳米抗体进行了广泛表征。对纳米材料进行了体外和体内应用测试。在体外和体内评估了该纳米系统的抑瘤效果。FDPM可以在磁引导下人工定向，同时继承CM的各种生物学功能。静脉注射后，FDPM通过磁吸引力被吸引到肿瘤部位，在CM的帮助下可以穿过血脑屏障。其同源靶向能力源于CM上的活性蛋白，使其能够特异性靶向GSCs和相关肿瘤细胞。纳米颗粒中包裹的阿霉素（DOX）随后破坏这些肿瘤细胞。FDPM表现出优异的生物相容性和肿瘤靶向效率，有效地靶向由GSCs引发的恶性胶质瘤。FDPM显著减少肿瘤细胞，抑制肿瘤生长，并显著延长荷瘤裸鼠的生存期。这些发现将FDPM定位为一种有前景的纳米平台，可靶向GSCs和相关肿瘤细胞以提高胶质瘤的治疗效果。
