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Optimization of Short RNA Aptamers for TNBC Cell Targeting

Triple-negative breast cancer (TNBC) is an aggressive cancer with limited targeted therapies. RNA aptamers, suitably chemically modified, work for therapeutic purposes in the same way as antibodies. We recently generated 2′Fluoro-pyrimidines RNA-aptamers that act as effective recognition elements fo...

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Detalles Bibliográficos
Autores principales: Camorani, Simona, d’Argenio, Annachiara, Agnello, Lisa, Nilo, Roberto, Zannetti, Antonella, Ibarra, Luis Exequiel, Fedele, Monica, Cerchia, Laura
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8998535/
https://www.ncbi.nlm.nih.gov/pubmed/35408872
http://dx.doi.org/10.3390/ijms23073511
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author Camorani, Simona
d’Argenio, Annachiara
Agnello, Lisa
Nilo, Roberto
Zannetti, Antonella
Ibarra, Luis Exequiel
Fedele, Monica
Cerchia, Laura
author_facet Camorani, Simona
d’Argenio, Annachiara
Agnello, Lisa
Nilo, Roberto
Zannetti, Antonella
Ibarra, Luis Exequiel
Fedele, Monica
Cerchia, Laura
author_sort Camorani, Simona
collection PubMed
description Triple-negative breast cancer (TNBC) is an aggressive cancer with limited targeted therapies. RNA aptamers, suitably chemically modified, work for therapeutic purposes in the same way as antibodies. We recently generated 2′Fluoro-pyrimidines RNA-aptamers that act as effective recognition elements for functional surface signatures of TNBC cells. Here, we optimized three of them by shortening and proved the truncated aptamers as optimal candidates to enable active targeting to TNBC. By using prediction of secondary structure to guide truncation, we identified structural regions that account for the binding motifs of the full-length aptamers. Their chemical synthesis led to short aptamers with superb nuclease resistance, which specifically bind to TNBC target cells and rapidly internalize into acidic compartments. They interfere with the growth of TNBC cells as mammospheres, thus confirming their potential as anti-tumor agents. We propose sTN145, sTN58 and sTN29 aptamers as valuable tools for selective TNBC targeting and promising candidates for effective treatments, including therapeutic agents and targeted delivery nanovectors.
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spelling pubmed-89985352022-04-12 Optimization of Short RNA Aptamers for TNBC Cell Targeting Camorani, Simona d’Argenio, Annachiara Agnello, Lisa Nilo, Roberto Zannetti, Antonella Ibarra, Luis Exequiel Fedele, Monica Cerchia, Laura Int J Mol Sci Article Triple-negative breast cancer (TNBC) is an aggressive cancer with limited targeted therapies. RNA aptamers, suitably chemically modified, work for therapeutic purposes in the same way as antibodies. We recently generated 2′Fluoro-pyrimidines RNA-aptamers that act as effective recognition elements for functional surface signatures of TNBC cells. Here, we optimized three of them by shortening and proved the truncated aptamers as optimal candidates to enable active targeting to TNBC. By using prediction of secondary structure to guide truncation, we identified structural regions that account for the binding motifs of the full-length aptamers. Their chemical synthesis led to short aptamers with superb nuclease resistance, which specifically bind to TNBC target cells and rapidly internalize into acidic compartments. They interfere with the growth of TNBC cells as mammospheres, thus confirming their potential as anti-tumor agents. We propose sTN145, sTN58 and sTN29 aptamers as valuable tools for selective TNBC targeting and promising candidates for effective treatments, including therapeutic agents and targeted delivery nanovectors. MDPI 2022-03-23 /pmc/articles/PMC8998535/ /pubmed/35408872 http://dx.doi.org/10.3390/ijms23073511 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
Camorani, Simona
d’Argenio, Annachiara
Agnello, Lisa
Nilo, Roberto
Zannetti, Antonella
Ibarra, Luis Exequiel
Fedele, Monica
Cerchia, Laura
Optimization of Short RNA Aptamers for TNBC Cell Targeting
title Optimization of Short RNA Aptamers for TNBC Cell Targeting
title_full Optimization of Short RNA Aptamers for TNBC Cell Targeting
title_fullStr Optimization of Short RNA Aptamers for TNBC Cell Targeting
title_full_unstemmed Optimization of Short RNA Aptamers for TNBC Cell Targeting
title_short Optimization of Short RNA Aptamers for TNBC Cell Targeting
title_sort optimization of short rna aptamers for tnbc cell targeting
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8998535/
https://www.ncbi.nlm.nih.gov/pubmed/35408872
http://dx.doi.org/10.3390/ijms23073511
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