Graphene nanoribbons as a drug delivery agent for lucanthone mediated therapy of glioblastoma multiforme

Nanomedicine. 2015 Jan;11(1):109-18. doi: 10.1016/j.nano.2014.08.001. Epub 2014 Aug 13.

Abstract

We report use of PEG-DSPE coated oxidized graphene nanoribbons (O-GNR-PEG-DSPE) as agent for delivery of anti-tumor drug Lucanthone (Luc) into Glioblastoma Multiformae (GBM) cells targeting base excision repair enzyme APE-1 (Apurinic endonuclease-1). Lucanthone, an endonuclease inhibitor of APE-1, was loaded onto O-GNR-PEG-DSPEs using a simple non-covalent method. We found its uptake by GBM cell line U251 exceeding 67% and 60% in APE-1-overexpressing U251, post 24h. However, their uptake was ~38% and 29% by MCF-7 and rat glial progenitor cells (CG-4), respectively. TEM analysis of U251 showed large aggregates of O-GNR-PEG-DSPE in vesicles. Luc-O-GNR-PEG-DSPE was significantly toxic to U251 but showed little/no toxicity when exposed to MCF-7/CG-4 cells. This differential uptake effect can be exploited to use O-GNR-PEG-DSPEs as a vehicle for Luc delivery to GBM, while reducing nonspecific cytotoxicity to the surrounding healthy tissue. Cell death in U251 was necrotic, probably due to oxidative degradation of APE-1.

Keywords: Apurinic endonuclease-1; CG-4; GBM; Graphene nanoribbons; Lucanthone; Rat glial progenitor cells; Thioxanthenones.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Brain Neoplasms / drug therapy*
  • Cell Line, Tumor
  • Coculture Techniques
  • DNA-(Apurinic or Apyrimidinic Site) Lyase / chemistry
  • Drug Delivery Systems*
  • Flow Cytometry
  • Glioblastoma / drug therapy*
  • Graphite / chemistry*
  • Humans
  • Hydrogen-Ion Concentration
  • Lucanthone / chemistry*
  • Mice
  • Microscopy, Electron, Transmission
  • Nanotubes, Carbon / chemistry
  • Neoplasm Transplantation
  • Neuroglia / metabolism
  • Oxygen / chemistry
  • Rats
  • Stem Cells / cytology

Substances

  • Nanotubes, Carbon
  • Graphite
  • Apex1 protein, rat
  • DNA-(Apurinic or Apyrimidinic Site) Lyase
  • Lucanthone
  • Oxygen