The Interaction Between Functionalized Graphene Oxide And Macrophage

Biological safety of nanomaterials directly determines its biomedical applications in the future. Due to its unique physicochemical properties, graphene oxide and its derivatives have shown great potential in biomedicine. The immune system plays crucial roles in protecting organisms, and in recent years, the immunological effects of GO and its derivatives have attracted a great of attentions. However, additional efforts are still needed. Considering the critical roles of macrophages in the innate immunity, we systematically investigated the interactions between macrophages and GO and its functionalized derivatives, as well as their possible mechanisms.Firstly, we investigated the effects of GO and PEGylated graphene oxide (GO-PEG) on the morphology and biological functions of murine macrophage RAW 264.7. It was shown that GO could significantly inhibit the cell proliferation and induce the formation of autophagosome, cytoplasm vacuolization and nucleus marginalization. Meanwhile, mRN A levels of multiple autophagy-related cytokines including TNF-α, IL-1β,IL-6 and IL-10 significantly changed after GO treatment, such as, IL-1β, IL-10 were down-regulated, IL-6 was up-regulated remarkably, TNF-α showed slight variation. Furthermore, GO could also induce the autophagy of other multiple kinds of cells such as murine macrophage Ana-1, murine peritoneal macrophages and murine embryonic fibroblasts NIH 3T3. It is interesting that, distinguished from GO, GO-PEG did not induce the autophagy of cells, which may be attributed to the decreased interactions between GO-PEG and cells.Above mentioned interesting results encourage us to uncover the underlying mechanisms through multiple assays involving signal pathway inhibitors, RNA interference technology, western blotting and flow cytometry. Consistent with other studies, Toll-like receptor 4 (TLR4) signaling pathway plays an important role in the GO induced autophagy. To our surprise, Toll-like receptor 3 (TLR3) signaling pathway also was essential in mediating autophagy of GO treated cells. The degree of cell autophagy significantly reduced after TLR3 silenced. This study reveals the mechanism of GO-mediated macrophage autophagy, and provide important theoretical support for in-depth exploration immunological effects of GO and its derivatives, especially the interaction mechanism with immune cells.