Glycyrrhetinic Acid Functionalized Graphene Oxide for Mitochondria Targeting and Cancer Treatment In Vivo

• DOI: 10.1002/smll.201703306
• Publication Date: 2017-12-05T10:39:54Z
• Authors: Chao Zhang; Zunfeng Liu; Ying Zheng; Yadi Geng; Chao Han; Yamin Shi; Hongbin Sun; Can Zhang; Yijun Chen; Luyong Zhang; Qinglong Guo; Lei Yang; Xiang Zhou; Lingyi Kong
• Keywords: Membrane Potential, Mitochondrial; Drug Carriers; 0303 health sciences; Cell Survival; Liver Neoplasms; Mice, Nude; Hep G2 Cells; Mitochondria; 3. Good health; Mice; 03 medical and health sciences; Drug Delivery Systems; Doxorubicin; Cell Line, Tumor; Animals; Glycyrrhetinic Acid; Humans; Graphite

AbstractMitochondria‐mediated apoptosis (MMA) is a preferential option for cancer therapy due to the presence of cell‐suicide factors in mitochondria, however, low permeability of mitochondria is a bottleneck for targeting drug delivery. In this paper, glycyrrhetinic acid (GA), a natural product from Glycyrrhiza glabra, is found to be a novel mitochondria targeting ligand, which can improve mitochondrial permeability and enhance the drug uptake of mitochondria. GA‐functionalized graphene oxide (GO) is prepared and used as an effective carrier for targeted delivery of doxorubicin into mitochondria. The detailed in vitro and in vivo mechanism study shows that GA‐functionalized GO causes a decrease in mitochondrial membrane potential and activates the MMA pathway. The GA‐functionalized drug delivery system demonstrates highly improved apoptosis induction ability and anticancer efficacy compared to the non‐GA‐functionalized nanocarrier delivery system. The GA‐functionalized nanocarrier also shows low toxicity, suggesting that it can be a useful tool for drug delivery.