Graphene Nanoribbons as a Drug Delivery Agent for Lucanthone Mediated Therapy of Glioblastoma Multiforme


Autoria(s): Chaudhary, Pankaj
Data(s)

12/08/2014

Resumo

<br/>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 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. Cell death in U251 was necrotic, probably due to oxidative degradation of APE-1.<br/><br/>Graphical abstract<br/><br/>We used O-GNR-PEG-DSPE as a reliable, non-toxic vehicle for delivery of APE-1 inhibiting Lucanthone into GBM tumor cell lines. LUC-O-GNR-PEG-DSPE particles showed 60% or more uptake by CMV/U251 and A1-5/CMV/U251 where as the uptake by MCF7 and normal CG4 glial cells was much lower (38% and 29% respectively). Different concentrations of Luc (5–80 μM) loaded onto O-GNR-PEG-DSPE showed lower toxicity in the exposed cells compared to the free drug, due to possible slow release of the drug from this particle, which ensures minimum non-specific release of the drug from the particle once it is injected in vivo.<br/>http://ars.els-cdn.com/content/image/1-s2.0-S1549963414004249-fx1.jpg<br/><br/>

Identificador

http://pure.qub.ac.uk/portal/en/publications/graphene-nanoribbons-as-a-drug-delivery-agent-for-lucanthone-mediated-therapy-of-glioblastoma-multiforme(0256d9e0-48b0-40da-8b9f-e97e09651000).html

http://dx.doi.org/10.1016/j.nano.2014.08.001

Idioma(s)

eng

Direitos

info:eu-repo/semantics/restrictedAccess

Fonte

Chaudhary , P 2014 , ' Graphene Nanoribbons as a Drug Delivery Agent for Lucanthone Mediated Therapy of Glioblastoma Multiforme ' Nanomedicine: Nanotechnology, Biology and Medicine , vol 11 , no. 1 , pp. 109-118 . DOI: 10.1016/j.nano.2014.08.001

Palavras-Chave #Nanoparticles, Graphene, Glioblastoma, Drug delivery, Tumor sensitization #/dk/atira/pure/subjectarea/asjc/1300/1306 #Cancer Research #/dk/atira/pure/subjectarea/asjc/3000/3002 #Drug Discovery
Tipo

article