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, García, Cristina Espinosa, Rodriguez, Miguel Ángel, Lopez, Diana, Perera, Ibon, Conlon, Kelly, Barrientos, Africa, Coulter, Tom, Pace, Alessandro, Hale, Sarah J. M., Ferrari, Enrico and Bachrati, Csanad Z. (2022) Targeting Ultrasmall Gold Nanoparticles with cRGD Peptide Increases the Uptake and Efficacy of Cytotoxic Payload. Nanomaterials, 12 (22). p. 4013. ISSN 2079-4991

Full content URL: https://doi.org/10.3390/nano12224013

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Targeting Ultrasmall Gold Nanoparticles with cRGD Peptide Increases the Uptake and Efficacy of Cytotoxic Payload
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Targeted ultrasmall gold nanoparticles increase the uptake and efficacy of cytotoxic payload
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Abstract

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.

Keywords:ultra-small gold nanoparticles, DM1, cRGD-peptide, ?V?3 integrin, targeted drug delivery
Subjects:C Biological Sciences > C560 Biotechnology
C Biological Sciences > C130 Cell Biology
C Biological Sciences > C700 Molecular Biology, Biophysics and Biochemistry
Divisions:College of Science > School of Life and Environmental Sciences > Department of Life Sciences
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ID Code:52432
Deposited On:22 Nov 2022 16:47

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