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New Clathrin-Based Nanoplatforms for Magnetic Resonance Imaging

BACKGROUND: 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-...

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Autores principales: Vitaliano, Gordana D., Vitaliano, Franco, Rios, Jose D., Renshaw, Perry F., Teicher, Martin H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3341379/
https://www.ncbi.nlm.nih.gov/pubmed/22563470
http://dx.doi.org/10.1371/journal.pone.0035821
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author Vitaliano, Gordana D.
Vitaliano, Franco
Rios, Jose D.
Renshaw, Perry F.
Teicher, Martin H.
author_facet Vitaliano, Gordana D.
Vitaliano, Franco
Rios, Jose D.
Renshaw, Perry F.
Teicher, Martin H.
author_sort Vitaliano, Gordana D.
collection PubMed
description BACKGROUND: 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±4.8: 1 for triskelia, and 4.2±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.
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spelling pubmed-33413792012-05-04 New Clathrin-Based Nanoplatforms for Magnetic Resonance Imaging Vitaliano, Gordana D. Vitaliano, Franco Rios, Jose D. Renshaw, Perry F. Teicher, Martin H. PLoS One Research Article BACKGROUND: 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±4.8: 1 for triskelia, and 4.2±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. Public Library of Science 2012-05-01 /pmc/articles/PMC3341379/ /pubmed/22563470 http://dx.doi.org/10.1371/journal.pone.0035821 Text en Vitaliano et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Vitaliano, Gordana D.
Vitaliano, Franco
Rios, Jose D.
Renshaw, Perry F.
Teicher, Martin H.
New Clathrin-Based Nanoplatforms for Magnetic Resonance Imaging
title New Clathrin-Based Nanoplatforms for Magnetic Resonance Imaging
title_full New Clathrin-Based Nanoplatforms for Magnetic Resonance Imaging
title_fullStr New Clathrin-Based Nanoplatforms for Magnetic Resonance Imaging
title_full_unstemmed New Clathrin-Based Nanoplatforms for Magnetic Resonance Imaging
title_short New Clathrin-Based Nanoplatforms for Magnetic Resonance Imaging
title_sort new clathrin-based nanoplatforms for magnetic resonance imaging
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3341379/
https://www.ncbi.nlm.nih.gov/pubmed/22563470
http://dx.doi.org/10.1371/journal.pone.0035821
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