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EGFR-Targeted Cellular Delivery of Therapeutic Nucleic Acids Mediated by Boron Clusters
New boron carriers with high boron content and targeted cancer-cell delivery are considered the first choice for boron neutron capture therapy (BNCT) for cancer treatment. Previously, we have shown that composites of antisense oligonucleotide and boron clusters are functional nanoparticles for the d...
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/PMC9740766/ https://www.ncbi.nlm.nih.gov/pubmed/36499115 http://dx.doi.org/10.3390/ijms232314793 |
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author | Kaniowski, Damian Suwara, Justyna Ebenryter-Olbińska, Katarzyna Jakóbik-Kolon, Agata Nawrot, Barbara |
author_facet | Kaniowski, Damian Suwara, Justyna Ebenryter-Olbińska, Katarzyna Jakóbik-Kolon, Agata Nawrot, Barbara |
author_sort | Kaniowski, Damian |
collection | PubMed |
description | New boron carriers with high boron content and targeted cancer-cell delivery are considered the first choice for boron neutron capture therapy (BNCT) for cancer treatment. Previously, we have shown that composites of antisense oligonucleotide and boron clusters are functional nanoparticles for the downregulation of expression of epidermal growth factor receptor (EGFR) and can be loaded into EGFR-overexpressing cancer cells without a transfection factor. In this study, we hypothesize that free cellular uptake is mediated by binding and activation of the EGFR by boron clusters. Proteomic analysis of proteins pulled-down from various EGFR-overexpressing cancer cells using short oligonucleotide probes, conjugated to 1,2-dicarba-closo-dodecaborane (1,2-DCDDB, [C(2)B(10)H(12)]) and [(3,3′-Iron-1,2,1′,2′-dicarbollide)(−)] (FESAN, [Fe(C(2)B(9)H(11))(2)](−)), evidenced that boron cage binds to EGFR subdomains. Moreover, inductively coupled plasma mass spectrometry (ICP MS) and fluorescence microscopy analyses confirmed that FESANs-highly decorated B-ASOs were efficiently delivered and internalized by EGFR-overexpressing cells. Antisense reduction of EGFR in A431 and U87-MG cells resulted in decreased boron accumulation compared to control cells, indicating that cellular uptake of B-ASOs is related to EGFR-dependent internalization. The data obtained suggest that EGFR-mediated cellular uptake of B-ASO represents a novel strategy for cellular delivery of therapeutic nucleic acids (and possibly other medicines) conjugated to boron clusters. |
format | Online Article Text |
id | pubmed-9740766 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-97407662022-12-11 EGFR-Targeted Cellular Delivery of Therapeutic Nucleic Acids Mediated by Boron Clusters Kaniowski, Damian Suwara, Justyna Ebenryter-Olbińska, Katarzyna Jakóbik-Kolon, Agata Nawrot, Barbara Int J Mol Sci Article New boron carriers with high boron content and targeted cancer-cell delivery are considered the first choice for boron neutron capture therapy (BNCT) for cancer treatment. Previously, we have shown that composites of antisense oligonucleotide and boron clusters are functional nanoparticles for the downregulation of expression of epidermal growth factor receptor (EGFR) and can be loaded into EGFR-overexpressing cancer cells without a transfection factor. In this study, we hypothesize that free cellular uptake is mediated by binding and activation of the EGFR by boron clusters. Proteomic analysis of proteins pulled-down from various EGFR-overexpressing cancer cells using short oligonucleotide probes, conjugated to 1,2-dicarba-closo-dodecaborane (1,2-DCDDB, [C(2)B(10)H(12)]) and [(3,3′-Iron-1,2,1′,2′-dicarbollide)(−)] (FESAN, [Fe(C(2)B(9)H(11))(2)](−)), evidenced that boron cage binds to EGFR subdomains. Moreover, inductively coupled plasma mass spectrometry (ICP MS) and fluorescence microscopy analyses confirmed that FESANs-highly decorated B-ASOs were efficiently delivered and internalized by EGFR-overexpressing cells. Antisense reduction of EGFR in A431 and U87-MG cells resulted in decreased boron accumulation compared to control cells, indicating that cellular uptake of B-ASOs is related to EGFR-dependent internalization. The data obtained suggest that EGFR-mediated cellular uptake of B-ASO represents a novel strategy for cellular delivery of therapeutic nucleic acids (and possibly other medicines) conjugated to boron clusters. MDPI 2022-11-26 /pmc/articles/PMC9740766/ /pubmed/36499115 http://dx.doi.org/10.3390/ijms232314793 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 Kaniowski, Damian Suwara, Justyna Ebenryter-Olbińska, Katarzyna Jakóbik-Kolon, Agata Nawrot, Barbara EGFR-Targeted Cellular Delivery of Therapeutic Nucleic Acids Mediated by Boron Clusters |
title | EGFR-Targeted Cellular Delivery of Therapeutic Nucleic Acids Mediated by Boron Clusters |
title_full | EGFR-Targeted Cellular Delivery of Therapeutic Nucleic Acids Mediated by Boron Clusters |
title_fullStr | EGFR-Targeted Cellular Delivery of Therapeutic Nucleic Acids Mediated by Boron Clusters |
title_full_unstemmed | EGFR-Targeted Cellular Delivery of Therapeutic Nucleic Acids Mediated by Boron Clusters |
title_short | EGFR-Targeted Cellular Delivery of Therapeutic Nucleic Acids Mediated by Boron Clusters |
title_sort | egfr-targeted cellular delivery of therapeutic nucleic acids mediated by boron clusters |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9740766/ https://www.ncbi.nlm.nih.gov/pubmed/36499115 http://dx.doi.org/10.3390/ijms232314793 |
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