title: Graphene nanoribbons as a drug delivery agent for lucanthone mediated therapy of glioblastoma multiforme.
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.
authors.affiliation: Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY, USA.
authors.forename: Sayan Mullick
authors.initials: SM
authors.lastname: Chowdhury
authors.affiliation: Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY, USA.
authors.forename: Cassandra
authors.initials: C
authors.lastname: Surhland
authors.affiliation: Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY, USA.
authors.forename: Zina
authors.initials: Z
authors.lastname: Sanchez
authors.affiliation: Centre for Cancer Research and Cell Biology, Queens University Belfast, Belfast, UK.
authors.forename: Pankaj
authors.initials: P
authors.lastname: Chaudhary
authors.affiliation: Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Suresh Kumar
authors.affiliation: Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY, USA; Biosciences Department, Brookhaven National Laboratory, Upton, NY, USA.
authors.forename: Louis A
authors.initials: LA
authors.lastname: Peña
authors.affiliation: Department of Pharmacology, Tennis Court Road, Cambridge University, Cambridge, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Waring
authors.affiliation: Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY, USA. Electronic address: balaji.sitharaman@stonybrook.edu.
authors.forename: Balaji
authors.initials: B
authors.lastname: Sitharaman
authors.affiliation: GeneSys Research Institute/Center for Cancer Systems Biology at Tufts School of Medicine, Boston, MA, USA. Electronic address: mamta.naidu@steward.org.
authors.forename: Mamta
authors.initials: M
authors.lastname: Naidu
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000737:chemistry; D016503:Drug Delivery Systems; D005434:Flow Cytometry; D005909:Glioblastoma / Q000188:drug therapy*; D006108:Graphite / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008154:Lucanthone / Q000737:chemistry*; D051379:Mice; D046529:Microscopy, Electron, Transmission; D037742:Nanotubes, Carbon / Q000737:chemistry; D009368:Neoplasm Transplantation; D009457:Neuroglia / Q000378:metabolism; D010100:Oxygen / Q000737:chemistry; D051381:Rats; D013234:Stem Cells / Q000166:cytology
chemical_list: D037742:Nanotubes, Carbon; D006108:Graphite; C470319:Apex1 protein, rat; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D008154:Lucanthone; D010100:Oxygen
keywords: Apurinic endonuclease-1; CG-4; GBM; Graphene nanoribbons; Lucanthone; Rat glial progenitor cells; Thioxanthenones