Promoting remyelination in multiple sclerosis is important to prevent axon degeneration, given the lack of curative treatment. Although some growth factors improve this repair, unspecific delivery to cells and potential side effects limit their therapeutic use. Thus, NFL-TBS.40-63 peptide (NFL)—known to enter specifically myelinating oligodendrocytes (OL)—was used to vectorize 100 nm diameter lipid nanoparticles (LNC), and the ability of NFL-LNC to specifically target OL from newborn rat brain was assessed in vitro. Specific uptake of DiD-labeled NFL-LNC by OL characterized by CNP and myelin basic protein was observed by confocal microscopy, as well as DiD colocalization with NFL and with Rab5—a marker of early endosomes. Unvectorized LNC did not significantly penetrate OL and there was no uptake of NFL-LNC by astrocytes. Canonical maturation of OL which extended compacted myelin-like membranes was observed by transmission electron microscopy in cells grown up to 9 days with NFL-LNC. Endocytosis of NFL-LNC appeared to depend on several pathways, as demonstrated by inhibitors. In addition, vectorized NFL-LNC adsorbed on neurotrophin-3 (NT-3) potentiated the proremyelinating effects of NT-3 after demyelination by lysophosphatidyl choline, allowing noticeably decreasing NT-3 concentration. Our results if they were confirmed in vivo suggest that NFL-vectorized LNC appear safe and could be considered as putative carriers for specific drug delivery to OL in order to increase remyelination.

鉴于缺乏治愈性治疗，促进多发性硬化症的髓鞘再生对于预防轴突变性很重要。尽管一些生长因子改善了这种修复，但对细胞的非特异性递送和潜在的副作用限制了它们的治疗用途。因此，NFL-TBS.40-63 肽 (NFL)——已知可特异性进入有髓鞘少突胶质细胞 (OL)——被用于矢量化 100 nm 直径的脂质纳米颗粒 (LNC)，以及 NFL-LNC 特异性靶向新生儿 OL 的能力大鼠脑在体外进行评估。通过共聚焦显微镜观察到以 CNP 和髓鞘碱性蛋白为特征的 OL 对 DiD 标记的 NFL-LNC 的特异性摄取，以及与 NFL 和早期内体标记物 Rab5 的 DiD 共定位。未矢量化的 LNC 没有显着穿透 OL，并且星形胶质细胞没有摄取 NFL-LNC。通过透射电子显微镜在用 NFL-LNC 生长 9 天的细胞中观察到 OL 的典型成熟，其扩展了致密的髓鞘样膜。正如抑制剂所证明的那样，NFL-LNC 的内吞作用似乎依赖于几种途径。此外，吸附在neurotrophin-3 (NT-3) 上的矢量化NFL-LNC 在溶血磷脂酰胆碱脱髓鞘后增强了NT-3 的原髓鞘形成作用，从而显着降低了NT-3 浓度。如果它们在体内得到证实，我们的结果表明 NFL 矢量化 LNC 似乎是安全的，并且可以被认为是向 OL 输送特定药物以增加髓鞘再生的推定载体。正如抑制剂所证明的那样，NFL-LNC 的内吞作用似乎依赖于几种途径。此外，吸附在neurotrophin-3 (NT-3) 上的矢量化NFL-LNC 在溶血磷脂酰胆碱脱髓鞘后增强了NT-3 的前髓鞘形成作用，从而显着降低了NT-3 浓度。如果它们在体内得到证实，我们的结果表明 NFL 矢量化 LNC 似乎是安全的，并且可以被认为是向 OL 输送特定药物以增加髓鞘再生的推定载体。正如抑制剂所证明的那样，NFL-LNC 的内吞作用似乎依赖于几种途径。此外，吸附在neurotrophin-3 (NT-3) 上的矢量化NFL-LNC 在溶血磷脂酰胆碱脱髓鞘后增强了NT-3 的原髓鞘形成作用，从而显着降低了NT-3 浓度。如果它们在体内得到证实，我们的结果表明 NFL 矢量化 LNC 似乎是安全的，并且可以被认为是向 OL 输送特定药物以增加髓鞘再生的推定载体。