Univ Angers, Inserm, CNRS, MINT, SFR ICAT, F-49000 Angers, France.
Univ Angers, Inserm, CNRS, MINT, SFR ICAT, F-49000 Angers, France; GlioCure, F-49000 Angers, France.
Int J Pharm. 2021 Aug 10;605:120811. doi: 10.1016/j.ijpharm.2021.120811. Epub 2021 Jun 16.
Glioblastomas are the most frequent and aggressive cancer of the nervous system. The standard treatment is composed of neurosurgery followed by radiotherapy and chemotherapy, but the median survival remains very low. The NFL-TBS.40-63 peptide, also known as NFL-peptide, is capable to specifically penetrating all glioblastoma cell lines tested so far (rat, mouse and human), where it alters their microtubule network. Consequently, the peptide inhibits selectively the in vitro cell division of glioblastoma cells and their tumor development in vivo. When lipid nanocapsules are functionalized with the NFL-peptide, their uptake is targeted into glioblastoma cells both in vitro and in vivo. Here, we evaluated the impact of the NFL-peptide on J3T cells derived from a canine spontaneous glioblastoma, and its activity when functionalized to nanocapsules. Both flow cytometry and confocal microscopy experiments indicate that the NFL-peptide interacts with these cells and affects their biology, but it cannot enter in cells. By functionalizing lipid nanoparticles with the NFL-peptide, their uptake is also increased, while the peptide stays outside. This investigation reveals similarities and major differences between these canine cells and other glioblastoma cells, which are important aspects to consider when using this type of drug delivery system or performing pre-clinical studies with this animal model.
胶质母细胞瘤是最常见和侵袭性最强的神经系统癌症。标准治疗包括神经外科手术,随后是放疗和化疗,但中位生存期仍然很低。NFL-TBS.40-63 肽,也称为 NFL 肽,能够特异性穿透迄今为止测试的所有胶质母细胞瘤细胞系(大鼠、小鼠和人类),在这些细胞中改变它们的微管网络。因此,该肽选择性地抑制胶质母细胞瘤细胞的体外细胞分裂及其体内肿瘤发展。当脂质纳米胶囊用 NFL 肽功能化时,它们在体外和体内都被靶向进入胶质母细胞瘤细胞。在这里,我们评估了 NFL 肽对源自犬自发性胶质母细胞瘤的 J3T 细胞的影响及其在功能化到纳米胶囊时的活性。流式细胞术和共聚焦显微镜实验均表明,NFL 肽与这些细胞相互作用并影响其生物学特性,但不能进入细胞。通过用 NFL 肽功能化脂质纳米颗粒,它们的摄取也增加了,而肽仍留在外面。这项研究揭示了这些犬科细胞与其他胶质母细胞瘤细胞之间的相似性和主要差异,这些是在使用这种类型的药物输送系统或使用这种动物模型进行临床前研究时需要考虑的重要方面。