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Targeting Ultrasmall Gold Nanoparticles with cRGD Peptide Increases the Uptake and Efficacy of Cytotoxic Payload

Cyclic arginyl-glycyl-aspartic acid peptide (cRGD) peptides show a high affinity towards αVβ3 integrin, a receptor overexpressed in many cancers. We aimed to combine the versatility of ultrasmall gold nanoparticles (usGNP) with the target selectivity of cRGD peptide for the directed delivery of a cy...

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Autores principales: Perrins, Richard D., McCarthy, Lee-Anne, Robinson, Angela, Spry, Kelly L., Cognet, Valentin, Ferreira, Avelino, Porter, John, Garcίa, Cristina Espinosa, Rodriguez, Miguel Ángel, Lopez, Diana, Perera, Ibon, Conlon, Kelly, Barrientos, Africa, Coulter, Tom, Pace, Alessandro, Hale, Sarah J. M., Ferrari, Enrico, Bachrati, Csanad Z.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9696180/
https://www.ncbi.nlm.nih.gov/pubmed/36432299
http://dx.doi.org/10.3390/nano12224013
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author Perrins, Richard D.
McCarthy, Lee-Anne
Robinson, Angela
Spry, Kelly L.
Cognet, Valentin
Ferreira, Avelino
Porter, John
Garcίa, Cristina Espinosa
Rodriguez, Miguel Ángel
Lopez, Diana
Perera, Ibon
Conlon, Kelly
Barrientos, Africa
Coulter, Tom
Pace, Alessandro
Hale, Sarah J. M.
Ferrari, Enrico
Bachrati, Csanad Z.
author_facet Perrins, Richard D.
McCarthy, Lee-Anne
Robinson, Angela
Spry, Kelly L.
Cognet, Valentin
Ferreira, Avelino
Porter, John
Garcίa, Cristina Espinosa
Rodriguez, Miguel Ángel
Lopez, Diana
Perera, Ibon
Conlon, Kelly
Barrientos, Africa
Coulter, Tom
Pace, Alessandro
Hale, Sarah J. M.
Ferrari, Enrico
Bachrati, Csanad Z.
author_sort Perrins, Richard D.
collection PubMed
description Cyclic arginyl-glycyl-aspartic acid peptide (cRGD) peptides show a high affinity towards αVβ3 integrin, a receptor overexpressed in many cancers. We aimed to combine the versatility of ultrasmall gold nanoparticles (usGNP) with the target selectivity of cRGD peptide for the directed delivery of a cytotoxic payload in a novel design. usGNPs were synthesized with a modified Brust-Schiffrin method and functionalized via amide coupling and ligand exchange and their uptake, intracellular trafficking, and toxicity were characterized. Our cRGD functionalized usGNPs demonstrated increased cellular uptake by αVβ3 integrin expressing cells, are internalized via clathrin-dependent endocytosis, accumulated in the lysosomes, and when loaded with mertansine led to increased cytotoxicity. Targeting via cRGD functionalization provides a mechanism to improve the efficacy, tolerability, and retention of therapeutic GNPs.
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spelling pubmed-96961802022-11-26 Targeting Ultrasmall Gold Nanoparticles with cRGD Peptide Increases the Uptake and Efficacy of Cytotoxic Payload Perrins, Richard D. McCarthy, Lee-Anne Robinson, Angela Spry, Kelly L. Cognet, Valentin Ferreira, Avelino Porter, John Garcίa, Cristina Espinosa Rodriguez, Miguel Ángel Lopez, Diana Perera, Ibon Conlon, Kelly Barrientos, Africa Coulter, Tom Pace, Alessandro Hale, Sarah J. M. Ferrari, Enrico Bachrati, Csanad Z. Nanomaterials (Basel) Article Cyclic arginyl-glycyl-aspartic acid peptide (cRGD) peptides show a high affinity towards αVβ3 integrin, a receptor overexpressed in many cancers. We aimed to combine the versatility of ultrasmall gold nanoparticles (usGNP) with the target selectivity of cRGD peptide for the directed delivery of a cytotoxic payload in a novel design. usGNPs were synthesized with a modified Brust-Schiffrin method and functionalized via amide coupling and ligand exchange and their uptake, intracellular trafficking, and toxicity were characterized. Our cRGD functionalized usGNPs demonstrated increased cellular uptake by αVβ3 integrin expressing cells, are internalized via clathrin-dependent endocytosis, accumulated in the lysosomes, and when loaded with mertansine led to increased cytotoxicity. Targeting via cRGD functionalization provides a mechanism to improve the efficacy, tolerability, and retention of therapeutic GNPs. MDPI 2022-11-15 /pmc/articles/PMC9696180/ /pubmed/36432299 http://dx.doi.org/10.3390/nano12224013 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Perrins, Richard D.
McCarthy, Lee-Anne
Robinson, Angela
Spry, Kelly L.
Cognet, Valentin
Ferreira, Avelino
Porter, John
Garcίa, Cristina Espinosa
Rodriguez, Miguel Ángel
Lopez, Diana
Perera, Ibon
Conlon, Kelly
Barrientos, Africa
Coulter, Tom
Pace, Alessandro
Hale, Sarah J. M.
Ferrari, Enrico
Bachrati, Csanad Z.
Targeting Ultrasmall Gold Nanoparticles with cRGD Peptide Increases the Uptake and Efficacy of Cytotoxic Payload
title Targeting Ultrasmall Gold Nanoparticles with cRGD Peptide Increases the Uptake and Efficacy of Cytotoxic Payload
title_full Targeting Ultrasmall Gold Nanoparticles with cRGD Peptide Increases the Uptake and Efficacy of Cytotoxic Payload
title_fullStr Targeting Ultrasmall Gold Nanoparticles with cRGD Peptide Increases the Uptake and Efficacy of Cytotoxic Payload
title_full_unstemmed Targeting Ultrasmall Gold Nanoparticles with cRGD Peptide Increases the Uptake and Efficacy of Cytotoxic Payload
title_short Targeting Ultrasmall Gold Nanoparticles with cRGD Peptide Increases the Uptake and Efficacy of Cytotoxic Payload
title_sort targeting ultrasmall gold nanoparticles with crgd peptide increases the uptake and efficacy of cytotoxic payload
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9696180/
https://www.ncbi.nlm.nih.gov/pubmed/36432299
http://dx.doi.org/10.3390/nano12224013
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