Dual-Targeting Gold Nanoparticles: Simultaneous Decoration with Ligands for Co-Transporters SGLT-1 and B<sup>0</sup>AT1

Sodium–glucose co-transporter 1 (SGLT1) and sodium-dependent neutral amino acid transporter (B<sup>0</sup>AT1) are mainly expressed on the membrane of enterocytes, a type of epithelial cell found in the intestines. In addition to their physiological role in the absorption of nutrients, a...

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Main Authors: Giuseppe D’Orazio, Marco Marradi, Barbara La Ferla
Format: Article
Language:English
Published: MDPI AG 2024-03-01
Series:Applied Sciences
Subjects:
Online Access:https://www.mdpi.com/2076-3417/14/6/2248
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author Giuseppe D’Orazio
Marco Marradi
Barbara La Ferla
author_facet Giuseppe D’Orazio
Marco Marradi
Barbara La Ferla
author_sort Giuseppe D’Orazio
collection DOAJ
description Sodium–glucose co-transporter 1 (SGLT1) and sodium-dependent neutral amino acid transporter (B<sup>0</sup>AT1) are mainly expressed on the membrane of enterocytes, a type of epithelial cell found in the intestines. In addition to their physiological role in the absorption of nutrients, a protective role in the integrity of the intestinal barrier has been established. The natural ligands of SGLT1 (<span style="font-variant: small-caps;">d</span>-glucose) and of B<sup>0</sup>AT1 (<span style="font-variant: small-caps;">l</span>-glutamine) can trigger a protective anti-inflammatory effect on the intestinal epithelium. The literature suggests the activation of common intracellular pathways upon engagement of the two transporters, whose functional forms are composed of oligomers or clusters. Simultaneous activation of these two co-transporters could lead to a potential multitarget and synergistic anti-inflammatory effect. Therefore, nanoplatforms containing multiple copies of the ligands could represent chemical tools to study the potential simultaneous activation of the two co-transporters. For these reasons, in this study, a set of different gold nanoparticles decorated with derivatives of <span style="font-variant: small-caps;">d</span>-glucose and of <span style="font-variant: small-caps;">l</span>-glutamine were designed and prepared. In particular, the synthesis of suitable sulfur-ending functionalized ligand derivatives, including a <i>C</i>-glucoside derivative, their anchoring to gold nanoparticles and their physical–chemical characterization have been carried out. The obtained nanostructures could represent promising multifunctional platforms for further investigation of the existence of possible multitarget and synergistic effects toward the two co-transporters SGLT1 and B<sup>0</sup>AT1.
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spelling doaj.art-4f88a79499684291862f8b31f72e310a2024-03-27T13:19:06ZengMDPI AGApplied Sciences2076-34172024-03-01146224810.3390/app14062248Dual-Targeting Gold Nanoparticles: Simultaneous Decoration with Ligands for Co-Transporters SGLT-1 and B<sup>0</sup>AT1Giuseppe D’Orazio0Marco Marradi1Barbara La Ferla2Department of Chemistry, Università degli Studi di Milano, Via C. Golgi 19, 20133 Milan, ItalyDepartment of Chemistry “Ugo Schiff”, Università degli Studi di Firenze, Via della Lastruccia 13, 50019 Sesto Fiorentino, ItalyDepartment of Earth and Environmental Sciences DISAT, Università degli Studi di Milano-Bicocca, Piazza della Scienza 1, 20126 Milan, ItalySodium–glucose co-transporter 1 (SGLT1) and sodium-dependent neutral amino acid transporter (B<sup>0</sup>AT1) are mainly expressed on the membrane of enterocytes, a type of epithelial cell found in the intestines. In addition to their physiological role in the absorption of nutrients, a protective role in the integrity of the intestinal barrier has been established. The natural ligands of SGLT1 (<span style="font-variant: small-caps;">d</span>-glucose) and of B<sup>0</sup>AT1 (<span style="font-variant: small-caps;">l</span>-glutamine) can trigger a protective anti-inflammatory effect on the intestinal epithelium. The literature suggests the activation of common intracellular pathways upon engagement of the two transporters, whose functional forms are composed of oligomers or clusters. Simultaneous activation of these two co-transporters could lead to a potential multitarget and synergistic anti-inflammatory effect. Therefore, nanoplatforms containing multiple copies of the ligands could represent chemical tools to study the potential simultaneous activation of the two co-transporters. For these reasons, in this study, a set of different gold nanoparticles decorated with derivatives of <span style="font-variant: small-caps;">d</span>-glucose and of <span style="font-variant: small-caps;">l</span>-glutamine were designed and prepared. In particular, the synthesis of suitable sulfur-ending functionalized ligand derivatives, including a <i>C</i>-glucoside derivative, their anchoring to gold nanoparticles and their physical–chemical characterization have been carried out. The obtained nanostructures could represent promising multifunctional platforms for further investigation of the existence of possible multitarget and synergistic effects toward the two co-transporters SGLT1 and B<sup>0</sup>AT1.https://www.mdpi.com/2076-3417/14/6/2248gold nanoparticlesmultivalencysodium–glucose co-transporter 1 (SGLT1)sodium–glutamine co-transporter 1 (B<sup>0</sup>AT1)glycoderivativesthiol–ene coupling
spellingShingle Giuseppe D’Orazio
Marco Marradi
Barbara La Ferla
Dual-Targeting Gold Nanoparticles: Simultaneous Decoration with Ligands for Co-Transporters SGLT-1 and B<sup>0</sup>AT1
Applied Sciences
gold nanoparticles
multivalency
sodium–glucose co-transporter 1 (SGLT1)
sodium–glutamine co-transporter 1 (B<sup>0</sup>AT1)
glycoderivatives
thiol–ene coupling
title Dual-Targeting Gold Nanoparticles: Simultaneous Decoration with Ligands for Co-Transporters SGLT-1 and B<sup>0</sup>AT1
title_full Dual-Targeting Gold Nanoparticles: Simultaneous Decoration with Ligands for Co-Transporters SGLT-1 and B<sup>0</sup>AT1
title_fullStr Dual-Targeting Gold Nanoparticles: Simultaneous Decoration with Ligands for Co-Transporters SGLT-1 and B<sup>0</sup>AT1
title_full_unstemmed Dual-Targeting Gold Nanoparticles: Simultaneous Decoration with Ligands for Co-Transporters SGLT-1 and B<sup>0</sup>AT1
title_short Dual-Targeting Gold Nanoparticles: Simultaneous Decoration with Ligands for Co-Transporters SGLT-1 and B<sup>0</sup>AT1
title_sort dual targeting gold nanoparticles simultaneous decoration with ligands for co transporters sglt 1 and b sup 0 sup at1
topic gold nanoparticles
multivalency
sodium–glucose co-transporter 1 (SGLT1)
sodium–glutamine co-transporter 1 (B<sup>0</sup>AT1)
glycoderivatives
thiol–ene coupling
url https://www.mdpi.com/2076-3417/14/6/2248
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AT marcomarradi dualtargetinggoldnanoparticlessimultaneousdecorationwithligandsforcotransporterssglt1andbsup0supat1
AT barbaralaferla dualtargetinggoldnanoparticlessimultaneousdecorationwithligandsforcotransporterssglt1andbsup0supat1