Cross-beta nanostructures based on dinaphthylalanine Gd-conjugates loaded with doxorubicin

Abstract Very recently we proposed novel di- and tetra-phenylalanine peptides derivatized with gadolinium complexes as potentials supramolecular diagnostic agents for applications in MRI (Magnetic Resonance Imaging). It was observed that in very short FF dipeptide building blocks, the propensity to...

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Autores principales:	Carlo Diaferia, Eliana Gianolio, Teresa Sibillano, Flavia Anna Mercurio, Marilisa Leone, Cinzia Giannini, Nicole Balasco, Luigi Vitagliano, Giancarlo Morelli, Antonella Accardo
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0d923f4b350141639b6f897d00f5a984
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spelling	oai:doaj.org-article:0d923f4b350141639b6f897d00f5a9842021-12-02T11:52:33ZCross-beta nanostructures based on dinaphthylalanine Gd-conjugates loaded with doxorubicin10.1038/s41598-017-00332-32045-2322https://doaj.org/article/0d923f4b350141639b6f897d00f5a9842017-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00332-3https://doaj.org/toc/2045-2322Abstract Very recently we proposed novel di- and tetra-phenylalanine peptides derivatized with gadolinium complexes as potentials supramolecular diagnostic agents for applications in MRI (Magnetic Resonance Imaging). It was observed that in very short FF dipeptide building blocks, the propensity to aggregate decreases significantly after modification with bulky moiety such as Gd-complexes, thus limiting their potential as CAs. We hypothesized that the replacement of the Phe side chain with more extended aromatic groups could improve the self-assembling. Here we describe the synthesis, structural and relaxometric behavior of a novel water soluble self-assembled peptide CA based on 2-naphthylalanine (2Nal). The peptide conjugate Gd-DOTA-L6-(2Nal)2 is able to self-assemble in long fibrillary nanostructures in water solution (up to 1.0 mg/mL). CD and FTIR spectroscopies indicate a β sheet secondary structure with an antiparallel orientation of single strands. All data are in good agreement with WAXS and SAXS characterizations that show the typical “cross-β pattern” for fibrils at the solid state. Molecular modeling indicates the three-dimensional structure of the peptide spine of aggregates is essentially constituted by extended β-sheet motifs stabilized by hydrogen bonds and hydrophobic interactions. The high relaxivity of nanoaggregates (12.3 mM−1 s−1 at 20 MHz) and their capability to encapsulate doxorubicin suggest their potential application as supramolecular theranostic agents.Carlo DiaferiaEliana GianolioTeresa SibillanoFlavia Anna MercurioMarilisa LeoneCinzia GianniniNicole BalascoLuigi VitaglianoGiancarlo MorelliAntonella AccardoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Carlo Diaferia Eliana Gianolio Teresa Sibillano Flavia Anna Mercurio Marilisa Leone Cinzia Giannini Nicole Balasco Luigi Vitagliano Giancarlo Morelli Antonella Accardo Cross-beta nanostructures based on dinaphthylalanine Gd-conjugates loaded with doxorubicin
description	Abstract Very recently we proposed novel di- and tetra-phenylalanine peptides derivatized with gadolinium complexes as potentials supramolecular diagnostic agents for applications in MRI (Magnetic Resonance Imaging). It was observed that in very short FF dipeptide building blocks, the propensity to aggregate decreases significantly after modification with bulky moiety such as Gd-complexes, thus limiting their potential as CAs. We hypothesized that the replacement of the Phe side chain with more extended aromatic groups could improve the self-assembling. Here we describe the synthesis, structural and relaxometric behavior of a novel water soluble self-assembled peptide CA based on 2-naphthylalanine (2Nal). The peptide conjugate Gd-DOTA-L6-(2Nal)2 is able to self-assemble in long fibrillary nanostructures in water solution (up to 1.0 mg/mL). CD and FTIR spectroscopies indicate a β sheet secondary structure with an antiparallel orientation of single strands. All data are in good agreement with WAXS and SAXS characterizations that show the typical “cross-β pattern” for fibrils at the solid state. Molecular modeling indicates the three-dimensional structure of the peptide spine of aggregates is essentially constituted by extended β-sheet motifs stabilized by hydrogen bonds and hydrophobic interactions. The high relaxivity of nanoaggregates (12.3 mM−1 s−1 at 20 MHz) and their capability to encapsulate doxorubicin suggest their potential application as supramolecular theranostic agents.
format	article
author	Carlo Diaferia Eliana Gianolio Teresa Sibillano Flavia Anna Mercurio Marilisa Leone Cinzia Giannini Nicole Balasco Luigi Vitagliano Giancarlo Morelli Antonella Accardo
author_facet	Carlo Diaferia Eliana Gianolio Teresa Sibillano Flavia Anna Mercurio Marilisa Leone Cinzia Giannini Nicole Balasco Luigi Vitagliano Giancarlo Morelli Antonella Accardo
author_sort	Carlo Diaferia
title	Cross-beta nanostructures based on dinaphthylalanine Gd-conjugates loaded with doxorubicin
title_short	Cross-beta nanostructures based on dinaphthylalanine Gd-conjugates loaded with doxorubicin
title_full	Cross-beta nanostructures based on dinaphthylalanine Gd-conjugates loaded with doxorubicin
title_fullStr	Cross-beta nanostructures based on dinaphthylalanine Gd-conjugates loaded with doxorubicin
title_full_unstemmed	Cross-beta nanostructures based on dinaphthylalanine Gd-conjugates loaded with doxorubicin
title_sort	cross-beta nanostructures based on dinaphthylalanine gd-conjugates loaded with doxorubicin
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/0d923f4b350141639b6f897d00f5a984
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Cross-beta nanostructures based on dinaphthylalanine Gd-conjugates loaded with doxorubicin

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