Uniform Small Graphene Oxide as an Efficient Cellular Nanocarrier for Immunostimulatory CpG Oligonucleotides

Graphene oxide (GO) has attracted more and more attention as a promising nanomaterial in biomedical research and applications. In this study, we explore the ability of GO as nanocarrier for synthetic DNA strands. Immunostimulatory CpG oligodeoxynucleotides (ODNs) are attached to Poly-L-Lysine (PLL) functionalized, polydisperse GO, or uniform small GO (sGO) nanosheets. Both types of GO-CpG ODN nanoconjugates can be delivered into murine Raw264.7 macrophages and possess immunostimulatory activity, while sGO-CpG appears to be a more efficient stimulator. In addition, sGO-CpG nanosheets exhibit higher cellular uptake but better biocompatibility compared to the larger GO-CpG counterpart. Furthermore, PLL functionalized sGO-CpG has higher immunostimulatory activity than azide functionalized sGO-CpG. Together, our studies provide evidence that sGO can be utilized as an ideal intracellular nanocarrier for synthetic single-stranded DNA, and sGO-PLL-CpG conjugates may serve as a potential proinflammatory therapeutic tool.