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.
Sayan Mullick Chowdhury  1 ,  Cassandra Surhland  1 ,  Zina Sanchez  2 ,  Pankaj Chaudhary  3 ,  M A Suresh Kumar  2 ,  Stephen Lee  1 ,  Louis A Peña  4 ,  Michael Waring  5 ,  Balaji Sitharaman  6 ,  Mamta Naidu  7
Affiliations
  • 1. Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY, USA.
  • 2. Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY, USA.
  • 3. Centre for Cancer Research and Cell Biology, Queens University Belfast, Belfast, UK.
  • 4. Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY, USA; Biosciences Department, Brookhaven National Laboratory, Upton, NY, USA.
  • 5. Department of Pharmacology, Tennis Court Road, Cambridge University, Cambridge, UK.
  • 6. Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY, USA. Electronic address: [email protected].
  • 7. GeneSys Research Institute/Center for Cancer Systems Biology at Tufts School of Medicine, Boston, MA, USA. Electronic address: [email protected].
PMID: 25131339 DOI: 10.1016/j.nano.2014.08.001
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.
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