Graphene nanoribbons as a drug delivery agent for lucanthone mediated therapy of glioblastoma multiforme
- Stony Brook Univ., NY (United States). Dept. of Biomedical Engineering
- Stony Brook Univ., NY (United States). Dept. of Pharmacological Sciences
- Queens Univ., Belfast, Ireland (United Kingdom). Centre for Cancer Research and Cell Biology
- Stony Brook Univ., NY (United States). Dept. of Biomedical Engineering; Brookhaven National Lab. (BNL), Upton, NY (United States). Biosciences Dept.
- Univ. of Cambridge (United Kingdom). Dept. of Pharmacology
- Tufts School of Medicine, Boston, MA (United States). GeneSys Research Institute/Center for Cancer Systems Biology
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.
- Research Organization:
- Brookhaven National Laboratory (BNL), Upton, NY (United States)
- Sponsoring Organization:
- USDOE Office of Science (SC), Biological and Environmental Research (BER)
- Grant/Contract Number:
- SC00112704; KP-1401020/MO-079; 1DP2OD007394-01
- OSTI ID:
- 1174110
- Report Number(s):
- BNL-107524-2015-JA; R&D Project: MO-079; KP1401020
- Journal Information:
- Nanomedicine: Nanotechnologoy, Biology, and Medicine, Vol. 11, Issue 1; ISSN 1549-9634
- Publisher:
- ElsevierCopyright Statement
- Country of Publication:
- United States
- Language:
- English
Web of Science
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