Neuronal uptake and intracellular superoxide scavenging of a fullerene (C60)-poly(2-oxazoline)s nanoformulation

Handle URI:
http://hdl.handle.net/10754/598966
Title:
Neuronal uptake and intracellular superoxide scavenging of a fullerene (C60)-poly(2-oxazoline)s nanoformulation
Authors:
Tong, Jing; Zimmerman, Matthew C.; Li, Shumin; Yi, Xiang; Luxenhofer, Robert; Jordan, Rainer; Kabanov, Alexander V.
Abstract:
Fullerene, the third allotrope of carbon, has been referred to as a "radical sponge" because of its powerful radical scavenging activities. However, the hydrophobicity and toxicity associated with fullerene limits its application as a therapeutic antioxidant. In the present study, we sought to overcome these limitations by generating water-soluble nanoformulations of fullerene (C(60)). Fullerene (C(60)) was formulated with poly(N-vinyl pyrrolidine) (PVP) or poly(2-alkyl-2-oxazoline)s (POx) homopolymer and random copolymer to form nano-complexes. These C(60)-polymer complexes were characterized by UV-vis spectroscopy, infrared spectroscopy (IR), dynamic light scattering (DLS), atomic force microscopy (AFM) and transmission electron microscopy (TEM). Cellular uptake and intracellular distribution of the selected formulations in catecholaminergic (CATH.a) neurons were examined by UV-vis spectroscopy, immunofluorescence and immunogold labeling. Electron paramagnetic resonance (EPR) spectroscopy was used to determine the ability of these C(60)-polymer complexes to scavenge superoxide. Their cytotoxicity was evaluated in three different cell lines. C(60)-POx and C(60)-PVP complexes exhibited similar physicochemical properties and antioxidant activities. C(60)-poly(2-ethyl-2-oxazoline) (PEtOx) complex, but not C(60)-PVP complex, were efficiently taken up by CATH.a neurons and attenuated the increase in intra-neuronal superoxide induced by angiotensin II (Ang II) stimulation. These results show that C(60)-POx complexes are non-toxic, neuronal cell permeable, superoxide scavenging antioxidants that might be promising candidates for the treatment of brain-related diseases associated with increased levels of superoxide.
Citation:
Tong J, Zimmerman MC, Li S, Yi X, Luxenhofer R, et al. (2011) Neuronal uptake and intracellular superoxide scavenging of a fullerene (C60)-poly(2-oxazoline)s nanoformulation. Biomaterials 32: 3654–3665. Available: http://dx.doi.org/10.1016/j.biomaterials.2011.01.068.
Publisher:
Elsevier BV
Journal:
Biomaterials
KAUST Grant Number:
KUK-F1-029-32
Issue Date:
May-2011
DOI:
10.1016/j.biomaterials.2011.01.068
PubMed ID:
21342705
PubMed Central ID:
PMC3085347
Type:
Article
ISSN:
0142-9612
Sponsors:
This study was supported by the Nanomaterials Core Facility of the Nebraska Center of Nanomedicine supported by NIH COBRE grant RR021937 (awarded to A.V.K.). We also gratefully acknowledge the assistances of UNMC Nanoimaging Core Facility and the Core Electron Microscopy Research Facility (CEMRF) in the AFM and TEM experiments and support by the King Abdullah University of Science and Technology (KAUST Award No. KUK-F1-029-32, partial salary support for R.L.).
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Full metadata record

DC FieldValue Language
dc.contributor.authorTong, Jingen
dc.contributor.authorZimmerman, Matthew C.en
dc.contributor.authorLi, Shuminen
dc.contributor.authorYi, Xiangen
dc.contributor.authorLuxenhofer, Roberten
dc.contributor.authorJordan, Raineren
dc.contributor.authorKabanov, Alexander V.en
dc.date.accessioned2016-02-25T13:44:36Zen
dc.date.available2016-02-25T13:44:36Zen
dc.date.issued2011-05en
dc.identifier.citationTong J, Zimmerman MC, Li S, Yi X, Luxenhofer R, et al. (2011) Neuronal uptake and intracellular superoxide scavenging of a fullerene (C60)-poly(2-oxazoline)s nanoformulation. Biomaterials 32: 3654–3665. Available: http://dx.doi.org/10.1016/j.biomaterials.2011.01.068.en
dc.identifier.issn0142-9612en
dc.identifier.pmid21342705en
dc.identifier.doi10.1016/j.biomaterials.2011.01.068en
dc.identifier.urihttp://hdl.handle.net/10754/598966en
dc.description.abstractFullerene, the third allotrope of carbon, has been referred to as a "radical sponge" because of its powerful radical scavenging activities. However, the hydrophobicity and toxicity associated with fullerene limits its application as a therapeutic antioxidant. In the present study, we sought to overcome these limitations by generating water-soluble nanoformulations of fullerene (C(60)). Fullerene (C(60)) was formulated with poly(N-vinyl pyrrolidine) (PVP) or poly(2-alkyl-2-oxazoline)s (POx) homopolymer and random copolymer to form nano-complexes. These C(60)-polymer complexes were characterized by UV-vis spectroscopy, infrared spectroscopy (IR), dynamic light scattering (DLS), atomic force microscopy (AFM) and transmission electron microscopy (TEM). Cellular uptake and intracellular distribution of the selected formulations in catecholaminergic (CATH.a) neurons were examined by UV-vis spectroscopy, immunofluorescence and immunogold labeling. Electron paramagnetic resonance (EPR) spectroscopy was used to determine the ability of these C(60)-polymer complexes to scavenge superoxide. Their cytotoxicity was evaluated in three different cell lines. C(60)-POx and C(60)-PVP complexes exhibited similar physicochemical properties and antioxidant activities. C(60)-poly(2-ethyl-2-oxazoline) (PEtOx) complex, but not C(60)-PVP complex, were efficiently taken up by CATH.a neurons and attenuated the increase in intra-neuronal superoxide induced by angiotensin II (Ang II) stimulation. These results show that C(60)-POx complexes are non-toxic, neuronal cell permeable, superoxide scavenging antioxidants that might be promising candidates for the treatment of brain-related diseases associated with increased levels of superoxide.en
dc.description.sponsorshipThis study was supported by the Nanomaterials Core Facility of the Nebraska Center of Nanomedicine supported by NIH COBRE grant RR021937 (awarded to A.V.K.). We also gratefully acknowledge the assistances of UNMC Nanoimaging Core Facility and the Core Electron Microscopy Research Facility (CEMRF) in the AFM and TEM experiments and support by the King Abdullah University of Science and Technology (KAUST Award No. KUK-F1-029-32, partial salary support for R.L.).en
dc.publisherElsevier BVen
dc.subjectAntioxidanten
dc.subjectFree radicalen
dc.subjectFullerene (C60)en
dc.subjectNeural cellen
dc.subjectPolyoxazolineen
dc.titleNeuronal uptake and intracellular superoxide scavenging of a fullerene (C60)-poly(2-oxazoline)s nanoformulationen
dc.typeArticleen
dc.identifier.journalBiomaterialsen
dc.identifier.pmcidPMC3085347en
dc.contributor.institutionCenter for Drug Delivery and Nanomedicine, University of Nebraska Medical Center, Omaha, NE 68198, USA.en
kaust.grant.numberKUK-F1-029-32en

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