title: Targeted imaging and induction of apoptosis of drug-resistant hepatoma cells by miR-122-loaded graphene-InP nanocompounds.
abstract: BACKGROUND
  Currently, graphene oxide has attracted growing attention as a drug delivery system due to its unique characteristics. Furthermore, utilization of microRNAs as biomarkers and therapeutic strategies would be particularly attractive because of their biological mechanisms and relatively low toxicity. Therefore, we have developed functionalized nanocompounds consisted of graphene oxide, quantum dots and microRNA, which induced cancer cells apoptosis along with targeted imaging.
  
  
  RESULTS
  In the present study, we synthesized a kind of graphene-P-gp loaded with miR-122-InP@ZnS quantum dots nanocomposites (GPMQNs) that, in the presence of glutathione, provides controlled release of miR-122. The miR-122 actively targeted liver tumor cells and induced their apoptosis, including drug-resistant liver tumor cells. We also explored the near-infrared fluorescence and potential utility for targeting imaging of InP@ZnS quantum dots. To further understand the molecular mechanism of GPMQNs-induced apoptosis of drug-resistant HepG2/ADM hepatoma cells, the relevant apoptosis proteins and signal pathways were explored in vitro and in vivo. Furthermore, near-infrared GPMQNs, which exhibited reduced photon scattering and auto-fluorescence, were applied for tumor imaging in vivo to allow for deep tissue penetration and three-dimensional imaging.
  
  
  CONCLUSIONS
  In conclusion, techniques using GPMQNs could provide a novel targeted treatment for liver cancer, which possessed properties of targeted imaging, low toxicity, and controlled release.
authors.affiliation: Department of Medical Imaging, Jingling Hospital, School of Medicine, Nanjing Universtiy, Nanjing, 210002, China.|Nanjing Maternity and Child Health Medical Institute, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, 210004, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zeng
authors.affiliation: Institute of Stomatology, Nanjing Medical University, Nanjing, 210029, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, 210029, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.affiliation: Institute of Stomatology, Nanjing Medical University, Nanjing, 210029, China.
authors.forename: Han
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Biochemistry, Qiannan Medical College for Nationalities, Duyun, 558000, China.
authors.forename: Xianyun
authors.initials: X
authors.lastname: Hu
authors.affiliation: Nanjing Maternity and Child Health Medical Institute, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, 210004, China.
authors.forename: Ziyi
authors.initials: Z
authors.lastname: Fu
authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, 210029, China. zhanggen123@126.com.
authors.forename: Gen
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Biomedical Engineering, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, 210029, China. sslb_112@hotmail.com.
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Medical Imaging, Jingling Hospital, School of Medicine, Nanjing Universtiy, Nanjing, 210002, China. cjr.luguangming@vip.163.com.
authors.forename: Guangming
authors.initials: G
authors.lastname: Lu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000627:therapeutic use; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000000981:diagnostic imaging / Q000188:drug therapy*; D016503:Drug Delivery Systems; D065546:Drug Liberation; D005456:Fluorescent Dyes / Q000737:chemistry; D006108:Graphite / Q000737:chemistry*; D056945:Hep G2 Cells; D006801:Humans; D021621:Imaging, Three-Dimensional; D007204:Indium / Q000737:chemistry*; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy*; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000627:therapeutic use*; D053761:Nanocomposites / Q000737:chemistry*; D010720:Phosphines / Q000737:chemistry*; D010789:Phototherapy; D045663:Quantum Dots / Q000737:chemistry; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D005456:Fluorescent Dyes; C531907:MIRN122 microRNA, human; D035683:MicroRNAs; D010720:Phosphines; D007204:Indium; D006108:Graphite; C090882:indium phosphide
keywords: Cell apoptosis; Graphene oxide; Liver cancer; MiR-122; Near infrared; Quantum dots