Department of Biomedical Engineering, Stony Brook University, Stony Brook, New York.
Department of Medicine and the Stony Brook Cancer Center, Health Science Center, Stony Brook University, Stony Brook, New York.
J Biomed Mater Res B Appl Biomater. 2020 Apr;108(3):1141-1156. doi: 10.1002/jbm.b.34465. Epub 2019 Aug 24.
The bioactive sphingolipid ceramide has many important roles in cell signaling processes, particularly in signaling programmed cell death in cancer. However, ceramide levels are often impaired in multi-drug resistant and radiation resistant cancers due to the dysregulation of ceramide metabolism. Restoration of ceramide levels through external delivery therefore represents a potential therapeutic target for the treatment of resistant cancers. However, as a lipid, ceramide is extremely hydrophobic and requires a delivery system to enter cells. Here we report the development of a method to load significant amounts of the long chain C and C ceramides onto oxidized graphene nanoribbons (O-GNRs) derived from carbon nanotubes. Using O-GNRs as a delivery system for these ceramides, we were able to induce significant biological effects in HeLa cells in conjunction with C ceramide and ultraviolet radiation treatment. However, we found that O-GNRs themselves exert significant biological effects and can interfere with the actions of these ceramides and ultraviolet treatment. Loading of ceramides onto O-GNRs did not have a significant effect on the entry of the nanoparticles into cells. Despite the need for further improvement, these data represent an important first step in the development of O-GNRs as a delivery system for long chain ceramides.
生物活性神经酰胺在细胞信号转导过程中具有许多重要作用,特别是在癌症的程序性细胞死亡信号转导中。然而,由于神经酰胺代谢的失调,多药耐药和辐射耐药的癌症中的神经酰胺水平通常受损。通过外部递送来恢复神经酰胺水平因此代表了治疗耐药性癌症的潜在治疗靶标。然而,作为一种脂质,神经酰胺是极其疏水的,需要一种输送系统来进入细胞。在这里,我们报告了一种在从碳纳米管衍生的氧化石墨烯纳米带(O-GNR)上加载大量长链 C 和 C 神经酰胺的方法。使用 O-GNR 作为这些神经酰胺的递送系统,我们能够在与 C 神经酰胺和紫外线辐射处理结合时在 HeLa 细胞中诱导显著的生物学效应。然而,我们发现 O-GNR 本身会发挥显著的生物学效应,并可能干扰这些神经酰胺和紫外线处理的作用。将神经酰胺加载到 O-GNR 上对纳米颗粒进入细胞的作用没有显著影响。尽管需要进一步改进,但这些数据代表了将 O-GNR 作为长链神经酰胺递送系统开发的重要第一步。