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dc.contributor.authorVitaliano, Franco
dc.contributor.authorVitaliano, Gordana Dragan
dc.contributor.authorRios, Jose D.
dc.contributor.authorRenshaw, Perry Franklin
dc.contributor.authorTeicher, Martin Hersch
dc.date.accessioned2013-03-05T15:37:49Z
dc.date.issued2012
dc.identifier.citationVitaliano, Gordana D., Franco Vitaliano, Jose D. Rios, Perry F. Renshaw, and Martin H. Teicher. 2012. New clathrin-based nanoplatforms for magnetic resonance imaging. PLoS ONE 7(5): e35821.en_US
dc.identifier.issn1932-6203en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:10364592
dc.description.abstractBackground: Magnetic Resonance Imaging (MRI) has high spatial resolution, but low sensitivity for visualization of molecular targets in the central nervous system (CNS). Our goal was to develop a new MRI method with the potential for non-invasive molecular brain imaging. We herein introduce new bio-nanotechnology approaches for designing CNS contrast media based on the ubiquitous clathrin cell protein. Methodology/Principal Findings: The first approach utilizes three-legged clathrin triskelia modified to carry 81 gadolinium chelates. The second approach uses clathrin cages self-assembled from triskelia and designed to carry 432 gadolinium chelates. Clathrin triskelia and cages were characterized by size, structure, protein concentration, and chelate and gadolinium contents. Relaxivity was evaluated at 0.47 T. A series of studies were conducted to ascertain whether fluorescent-tagged clathrin nanoplatforms could cross the blood brain barriers (BBB) unaided following intranasal, intravenous, and intraperitoneal routes of administration. Clathrin nanoparticles can be constituted as triskelia (18.5 nm in size), and as cages assembled from them (55 nm). The mean chelate: clathrin heavy chain molar ratio was 27.04 \(\pm\) 4.8: 1 for triskelia, and 4.2 \(\pm\) 1.04: 1 for cages. Triskelia had ionic relaxivity of 16 mM\(^{−1}\)s\(^{−1}\), and molecular relaxivity of 1,166 mM\(^{−1}\)s\(^{−1}\), while cages had ionic relaxivity of 81 mM\(^{−1}\)s\(^{−1}\) and molecular relaxivity of 31,512 mM\(^{−1}\)s\(^{−1}\). Thus, cages exhibited 20 times higher ionic relaxivity and 8,000-fold greater molecular relaxivity than gadopentetate dimeglumine. Clathrin nanoplatforms modified with fluorescent tags were able to cross or bypass the BBB without enhancements following intravenous, intraperitoneal and intranasal administration in rats. Conclusions/Significance: Use of clathrin triskelia and cages as carriers of CNS contrast media represents a new approach. This new biocompatible protein-based nanotechnology demonstrated suitable physicochemical properties to warrant further in vivo imaging and drug delivery studies. Significantly, both nanotransporters crossed and/or bypassed the BBB without enhancers. Thus, clathrin nanoplatforms could be an appealing alternative to existing CNS bio-nanotechnologies.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.pone.0035821en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3341379/pdf/en_US
dash.licenseLAA
dc.subjectBiologyen_US
dc.subjectBiotechnologyen_US
dc.subjectBionanotechnologyen_US
dc.subjectNeuroscienceen_US
dc.subjectNeuroimagingen_US
dc.subjectChemistryen_US
dc.subjectChemical Reactionsen_US
dc.subjectChelationen_US
dc.subjectMaterials Scienceen_US
dc.subjectMaterial by Attributeen_US
dc.subjectNanomaterialsen_US
dc.subjectNanotechnologyen_US
dc.subjectMedicineen_US
dc.subjectDiagnostic Medicineen_US
dc.subjectRadiologyen_US
dc.subjectDiagnostic Radiologyen_US
dc.subjectMagnetic Resonance Imagingen_US
dc.titleNew Clathrin-Based Nanoplatforms for Magnetic Resonance Imagingen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS ONEen_US
dash.depositing.authorTeicher, Martin Hersch
dc.date.available2013-03-05T15:37:49Z
dc.identifier.doi10.1371/journal.pone.0035821*
dash.authorsorderedfalse
dash.contributor.affiliatedVitaliano, Gordana
dash.contributor.affiliatedRenshaw, Perry Franklin
dash.contributor.affiliatedTeicher, Martin


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