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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...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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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. |
format | Online Article Text |
id | pubmed-9696180 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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