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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2023
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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. |
format | Online Article Text |
id | pubmed-10460053 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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