胶质母细胞瘤是最常见和最具侵袭性的脑肿瘤。目前的治疗方法无法治愈患者。这在一定程度上归因于血脑屏障，它限制了药物输送到病变部位。为了克服这个问题，我们开发了功能化神经丝蛋白衍生肽NFL-TBS.40-63（NFL）的脂质体。NFL以其高度选择性的靶向胶质母细胞瘤细胞而闻名。首先，我们开发了体外血脑屏障模型，以检查NFL是否除了具有其主动靶向能力外，还可以促进屏障穿越。渗透性实验表明NFL肽能够穿越血脑屏障。此外，当血脑屏障处于病理状态即体外血脑肿瘤屏障时，NFL肽的通过度增加，同时保持其靶向胶质母细胞瘤的能力。当NFL肽与脂质体结合时，与不含NFL的脂质体相比，它增强了脂质体通过血脑肿瘤屏障后内吞入胶质母细胞瘤细胞的能力。与胶质母细胞瘤相比，脂质体在内皮细胞单层中的细胞内摄取受限。这些数据表明，当与药物输送系统结合时，NFL肽是一种有前景的细胞穿透肽工具，用于胶质母细胞瘤的治疗。版权所有 © 2023 Elsevier B.V. 发表。

Glioblastoma is the most common and aggressive brain tumor. Current treatments do not allow to cure the patients. This is partly due to the blood-brain barrier (BBB), which limits the delivery of drugs to the pathological site. To overcome this, we developed liposomes functionalized with a neurofilament-derived peptide, NFL-TBS.40-63 (NFL), known for its highly selective targeting of glioblastoma cells. First, in vitro BBB model was developed to check whether the NFL can also promote barrier crossing in addition to its active targeting capacity. Permeability experiments showed that the NFL peptide was able to cross the BBB. Moreover, when the BBB was in a pathological situation, i.e., an in vitro blood-brain tumor barrier (BBTB), the passage of the NFL peptide was greater while maintaining its glioblastoma targeting capacity. When the NFL peptide was associated to liposomes, it enhanced their ability to be internalized into glioblastoma cells after passage through the BBTB, compared to liposomes without NFL. The cellular uptake of liposomes was limited in the endothelial cell monolayer in comparison to the glioblastoma one. These data indicated that the NFL peptide is a promising cell-penetrating peptide tool when combined with drug delivery systems for the treatment of glioblastoma.Copyright © 2023. Published by Elsevier B.V.