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Cationic Calix[4]arene Vectors to Efficiently Deliver AntimiRNA Peptide Nucleic Acids (PNAs) and miRNA Mimics

One of the most appealing approaches for regulating gene expression, named the “microRNA therapeutic” method, is based on the regulation of the activity of microRNAs (miRNAs), the intracellular levels of which are dysregulated in many diseases, including cancer. This can be achieved by miRNA inhibit...

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Autores principales: Gasparello, Jessica, Papi, Chiara, Zurlo, Matteo, Volpi, Stefano, Gambari, Roberto, Corradini, Roberto, Casnati, Alessandro, Sansone, Francesco, Finotti, Alessia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10460053/
https://www.ncbi.nlm.nih.gov/pubmed/37631335
http://dx.doi.org/10.3390/pharmaceutics15082121
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author Gasparello, Jessica
Papi, Chiara
Zurlo, Matteo
Volpi, Stefano
Gambari, Roberto
Corradini, Roberto
Casnati, Alessandro
Sansone, Francesco
Finotti, Alessia
author_facet Gasparello, Jessica
Papi, Chiara
Zurlo, Matteo
Volpi, Stefano
Gambari, Roberto
Corradini, Roberto
Casnati, Alessandro
Sansone, Francesco
Finotti, Alessia
author_sort Gasparello, Jessica
collection PubMed
description One of the most appealing approaches for regulating gene expression, named the “microRNA therapeutic” method, is based on the regulation of the activity of microRNAs (miRNAs), the intracellular levels of which are dysregulated in many diseases, including cancer. This can be achieved by miRNA inhibition with antimiRNA molecules in the case of overexpressed microRNAs, or by using miRNA-mimics to restore downregulated microRNAs that are associated with the target disease. The development of new efficient, low-toxic, and targeted vectors of such molecules represents a key topic in the field of the pharmacological modulation of microRNAs. We compared the delivery efficiency of a small library of cationic calix[4]arene vectors complexed with fluorescent antimiRNA molecules (Peptide Nucleic Acids, PNAs), pre-miRNA (microRNA precursors), and mature microRNAs, in glioma- and colon-cancer cellular models. The transfection was assayed by cytofluorimetry, cell imaging assays, and RT-qPCR. The calix[4]arene-based vectors were shown to be powerful tools to facilitate the uptake of both neutral (PNAs) and negatively charged (pre-miRNAs and mature microRNAs) molecules showing low toxicity in transfected cells and ability to compete with commercially available vectors in terms of delivery efficiency. These results could be of great interest to validate microRNA therapeutics approaches for future application in personalized treatment and precision medicine.
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spelling pubmed-104600532023-08-27 Cationic Calix[4]arene Vectors to Efficiently Deliver AntimiRNA Peptide Nucleic Acids (PNAs) and miRNA Mimics Gasparello, Jessica Papi, Chiara Zurlo, Matteo Volpi, Stefano Gambari, Roberto Corradini, Roberto Casnati, Alessandro Sansone, Francesco Finotti, Alessia Pharmaceutics Article One of the most appealing approaches for regulating gene expression, named the “microRNA therapeutic” method, is based on the regulation of the activity of microRNAs (miRNAs), the intracellular levels of which are dysregulated in many diseases, including cancer. This can be achieved by miRNA inhibition with antimiRNA molecules in the case of overexpressed microRNAs, or by using miRNA-mimics to restore downregulated microRNAs that are associated with the target disease. The development of new efficient, low-toxic, and targeted vectors of such molecules represents a key topic in the field of the pharmacological modulation of microRNAs. We compared the delivery efficiency of a small library of cationic calix[4]arene vectors complexed with fluorescent antimiRNA molecules (Peptide Nucleic Acids, PNAs), pre-miRNA (microRNA precursors), and mature microRNAs, in glioma- and colon-cancer cellular models. The transfection was assayed by cytofluorimetry, cell imaging assays, and RT-qPCR. The calix[4]arene-based vectors were shown to be powerful tools to facilitate the uptake of both neutral (PNAs) and negatively charged (pre-miRNAs and mature microRNAs) molecules showing low toxicity in transfected cells and ability to compete with commercially available vectors in terms of delivery efficiency. These results could be of great interest to validate microRNA therapeutics approaches for future application in personalized treatment and precision medicine. MDPI 2023-08-10 /pmc/articles/PMC10460053/ /pubmed/37631335 http://dx.doi.org/10.3390/pharmaceutics15082121 Text en © 2023 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
Gasparello, Jessica
Papi, Chiara
Zurlo, Matteo
Volpi, Stefano
Gambari, Roberto
Corradini, Roberto
Casnati, Alessandro
Sansone, Francesco
Finotti, Alessia
Cationic Calix[4]arene Vectors to Efficiently Deliver AntimiRNA Peptide Nucleic Acids (PNAs) and miRNA Mimics
title Cationic Calix[4]arene Vectors to Efficiently Deliver AntimiRNA Peptide Nucleic Acids (PNAs) and miRNA Mimics
title_full Cationic Calix[4]arene Vectors to Efficiently Deliver AntimiRNA Peptide Nucleic Acids (PNAs) and miRNA Mimics
title_fullStr Cationic Calix[4]arene Vectors to Efficiently Deliver AntimiRNA Peptide Nucleic Acids (PNAs) and miRNA Mimics
title_full_unstemmed Cationic Calix[4]arene Vectors to Efficiently Deliver AntimiRNA Peptide Nucleic Acids (PNAs) and miRNA Mimics
title_short Cationic Calix[4]arene Vectors to Efficiently Deliver AntimiRNA Peptide Nucleic Acids (PNAs) and miRNA Mimics
title_sort cationic calix[4]arene vectors to efficiently deliver antimirna peptide nucleic acids (pnas) and mirna mimics
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10460053/
https://www.ncbi.nlm.nih.gov/pubmed/37631335
http://dx.doi.org/10.3390/pharmaceutics15082121
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