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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 24 hours (h). 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. In conclusion, cell death in U251 was necrotic, probably due to oxidative degradation of APE-1.

Authors:
 [1];  [1];  [2];  [3];  [2];  [1];  [4];  [5];  [1]; ORCiD logo [6]
  1. Stony Brook Univ., NY (United States). Dept. of Biomedical Engineering
  2. Stony Brook Univ., NY (United States). Dept. of Pharmacological Sciences
  3. Queens Univ., Belfast, Ireland (United Kingdom). Centre for Cancer Research and Cell Biology
  4. Stony Brook Univ., NY (United States). Dept. of Biomedical Engineering; Brookhaven National Lab. (BNL), Upton, NY (United States). Biosciences Dept.
  5. Univ. of Cambridge (United Kingdom). Dept. of Pharmacology
  6. Tufts School of Medicine, Boston, MA (United States). GeneSys Research Institute/Center for Cancer Systems Biology
Publication Date:
Research Org.:
Brookhaven National Laboratory (BNL), Upton, NY (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23)
OSTI Identifier:
1174110
Report Number(s):
BNL-107524-2015-JA
Journal ID: ISSN 1549-9634; R&D Project: MO-079; KP1401020
Grant/Contract Number:
SC00112704; KP-1401020/MO-079; 1DP2OD007394-01
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
Nanomedicine: Nanotechnologoy, Biology, and Medicine
Additional Journal Information:
Journal Volume: 11; Journal Issue: 1; Journal ID: ISSN 1549-9634
Publisher:
Elsevier
Country of Publication:
United States
Language:
English
Subject:
38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEAR CHEMISTRY; Apurinic endonuclease-1; Thioxanthenones; Luanthone; Graphene nanoribbons; GBM; CG-4; Rat glial progenitor cells

Citation Formats

Chowdhury, Sayan Mullick, Surhland, Cassandra, Sanchez, Zina, Chaudhary, Pankaj, Suresh Kumar, M. A., Lee, Stephen, Peña, Louis A., Waring, Michael, Sitharaman, Balaji, and Naidu, Mamta. Graphene nanoribbons as a drug delivery agent for lucanthone mediated therapy of glioblastoma multiforme. United States: N. p., 2014. Web. doi:10.1016/j.nano.2014.08.001.
Chowdhury, Sayan Mullick, Surhland, Cassandra, Sanchez, Zina, Chaudhary, Pankaj, Suresh Kumar, M. A., Lee, Stephen, Peña, Louis A., Waring, Michael, Sitharaman, Balaji, & Naidu, Mamta. Graphene nanoribbons as a drug delivery agent for lucanthone mediated therapy of glioblastoma multiforme. United States. doi:10.1016/j.nano.2014.08.001.
Chowdhury, Sayan Mullick, Surhland, Cassandra, Sanchez, Zina, Chaudhary, Pankaj, Suresh Kumar, M. A., Lee, Stephen, Peña, Louis A., Waring, Michael, Sitharaman, Balaji, and Naidu, Mamta. Wed . "Graphene nanoribbons as a drug delivery agent for lucanthone mediated therapy of glioblastoma multiforme". United States. doi:10.1016/j.nano.2014.08.001. https://www.osti.gov/servlets/purl/1174110.
@article{osti_1174110,
title = {Graphene nanoribbons as a drug delivery agent for lucanthone mediated therapy of glioblastoma multiforme},
author = {Chowdhury, Sayan Mullick and Surhland, Cassandra and Sanchez, Zina and Chaudhary, Pankaj and Suresh Kumar, M. A. and Lee, Stephen and Peña, Louis A. and Waring, Michael and Sitharaman, Balaji and Naidu, Mamta},
abstractNote = {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 24 hours (h). 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. In conclusion, cell death in U251 was necrotic, probably due to oxidative degradation of APE-1.},
doi = {10.1016/j.nano.2014.08.001},
journal = {Nanomedicine: Nanotechnologoy, Biology, and Medicine},
number = 1,
volume = 11,
place = {United States},
year = {Wed Aug 13 00:00:00 EDT 2014},
month = {Wed Aug 13 00:00:00 EDT 2014}
}

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Cited by: 19works
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