Delivery of long chain C16 and C24 ceramide in HeLa cells using oxidized graphene nanoribbons.

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 C16 and C24 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 C6 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.