壳聚糖纳米粒介导乳铁蛋白的核质转染及其对胶质瘤的作用：细胞定位依赖性的乳铁蛋白作用。
Nuclear and cytoplasmic delivery of lactoferrin in glioma using chitosan nanoparticles: Cellular location dependent-action of lactoferrin.
机构信息
Laboratory of Pharmaceutical Technology and Biopharmaceutics, University of Bonn, Bonn 53121, Germany; Department of Chemistry, The American University in Cairo, Cairo 11835, Egypt.
Department of Chemistry, The American University in Cairo, Cairo 11835, Egypt.
出版信息
Eur J Pharm Biopharm. 2018 Aug;129:74-79. doi: 10.1016/j.ejpb.2018.05.027. Epub 2018 May 23.
Lactoferrin (Lf) exerts anti-cancer effects on glioma, however, the exact mechanism remains unclear. Despite possessing a nuclear localization sequence (NLS), Lf was found to allocate only in the cytoplasm of glioma 261. Lf was therefore loaded into nuclear and cytoplasmic targeted nanoparticles (NPs) to determine whether nuclear delivery of Lf would enhance its anti-cancer effect. Upon treatment with 300 and 800 µg/mL Lf loaded chitosan NPs, nuclear targeted Lf-NPs showed 1.3 and 2.7 folds increase in cell viability, whereas cytoplasmic targeted Lf-NPs at 300 µg/mL decreased cell viability by 0.8 folds in comparison to free Lf and controls. Results suggest that the cytotoxicity of Lf on glioma is attributable to its cytoplasmic allocation. Nuclear delivery of Lf induced cell proliferation rather than cytotoxicity, indicating that the mode of action of Lf in glioma is cell location dependent. This calls for caution about the general use of Lf as an anti-cancer protein.
乳铁蛋白（Lf）对神经胶质瘤具有抗癌作用，但确切的机制尚不清楚。尽管乳铁蛋白具有核定位序列（NLS），但研究发现它仅分配在神经胶质瘤 261 的细胞质中。因此，将乳铁蛋白装载到核和细胞质靶向纳米颗粒（NPs）中，以确定核内递送乳铁蛋白是否会增强其抗癌作用。用 300 和 800μg/mL 装载壳聚糖 NPs 的乳铁蛋白处理后，核靶向 Lf-NPs 的细胞活力分别增加了 1.3 倍和 2.7 倍，而细胞质靶向 Lf-NPs 在 300μg/mL 时与游离 Lf 和对照相比，细胞活力降低了 0.8 倍。结果表明，Lf 对神经胶质瘤的细胞毒性归因于其细胞质分配。Lf 的核内递送诱导细胞增殖而不是细胞毒性，表明 Lf 在神经胶质瘤中的作用模式取决于细胞位置。这提醒人们要谨慎将 Lf 作为抗癌蛋白的一般用途。
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