NanoBioCel Group, University of the Basque Country (UPV/EHU), Vitoria-Gasteiz 01006, Spain.
Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid 28029, Spain.
Mol Pharm. 2020 Jun 1;17(6):1848-1858. doi: 10.1021/acs.molpharmaceut.9b01213. Epub 2020 Apr 29.
Gene therapy employing nanocarriers represents a promising strategy to treat central nervous system (CNS) diseases, where brain microvasculature is frequently compromised. Vascular endothelial growth factor (VEGF) is a key angiogenic molecule; however, its administration to the CNS by nonviral gene therapy has not been conducted. Hence, we prepared and physicochemically characterized four cationic niosome formulations (-), which were combined with pVEGF-GFP to explore their capacity to transfer the VEGF gene to CNS cells and achieve angiogenesis in the brain. Experiments in primary neuronal cells showed successful and safe transfection with niosome , producing double levels of biologically active VEGF in comparison to the rest of the formulations. Intracortical administration of niosome based nioplexes in mouse brain validated the ability of this nonviral vector to deliver the VEGF gene to CNS cells, inducing brain angiogenesis and emerging as a promising therapeutic approach for the treatment of CNS diseases.
采用纳米载体的基因治疗是治疗中枢神经系统（CNS）疾病的一种很有前途的策略，因为 CNS 的血管经常受损。血管内皮生长因子（VEGF）是一种关键的血管生成分子；然而，通过非病毒基因治疗将其递送到 CNS 中尚未进行。因此，我们制备并物理化学表征了四种阳离子脂质体配方（-），将其与 pVEGF-GFP 结合，以探索它们将 VEGF 基因转移到 CNS 细胞并在大脑中实现血管生成的能力。在原代神经元细胞中的实验表明，脂质体能够成功且安全地转染，与其他配方相比，产生了两倍水平的具有生物活性的 VEGF。脂质体基的 nioplexes 在小鼠大脑中的皮质内给药验证了这种非病毒载体将 VEGF 基因递送到 CNS 细胞的能力，诱导大脑血管生成，并成为治疗 CNS 疾病的有前途的治疗方法。
