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Novel Histone-Based DNA Carrier Targeting Cancer-Associated Fibroblasts
Nuclear proteins, like histone H2A, are promising non-viral carriers for gene delivery since they are biocompatible, biodegradable, bear intrinsic nuclear localization signal, and are easy to modify. The addition of surface-protein-binding ligand to histone H2A may increase its DNA delivery efficien...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464289/ https://www.ncbi.nlm.nih.gov/pubmed/32751200 http://dx.doi.org/10.3390/polym12081695 |
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author | Kuzmich, Alexey Rakitina, Olga Didych, Dmitry Potapov, Victor Zinovyeva, Marina Alekseenko, Irina Sverdlov, Eugene |
author_facet | Kuzmich, Alexey Rakitina, Olga Didych, Dmitry Potapov, Victor Zinovyeva, Marina Alekseenko, Irina Sverdlov, Eugene |
author_sort | Kuzmich, Alexey |
collection | PubMed |
description | Nuclear proteins, like histone H2A, are promising non-viral carriers for gene delivery since they are biocompatible, biodegradable, bear intrinsic nuclear localization signal, and are easy to modify. The addition of surface-protein-binding ligand to histone H2A may increase its DNA delivery efficiency. Tumor microenvironment (TME) is a promising target for gene therapy since its surface protein repertoire is more stable than that of cancer cells. Cancer-associated fibroblasts (CAFs) are important components of TME, and one of their surface markers is beta-type platelet-derived growth factor receptor (PDGFRβ). In this study, we fused histone H2A with PDGFRβ-binding peptide, YG2, to create a novel non-viral fibroblast-targeting DNA carrier, H2A-YG2. The transfection efficiency of histone complexes with pDNA encoding a bicistronic reporter (enhanced green fluorescent protein, EGFP, and firefly luciferase) in PDGFRβ-positive and PDGFRβ-negative cells was estimated by luciferase assay and flow cytometry. The luciferase activity, percentage of transfected cells, and overall EGFP fluorescence were increased due to histone modification with YG2 only in PDGFRβ-positive cells. We also estimated the internalization efficiency of DNA-carrier complexes using tetramethyl-rhodamine-labeled pDNA. The ligand fusion increased DNA internalization only in the PDGFRβ-positive cells. In conclusion, we demonstrated that the H2A-YG2 carrier targeted gene delivery to PDGFRβ-positive tumor stromal cells. |
format | Online Article Text |
id | pubmed-7464289 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-74642892020-09-04 Novel Histone-Based DNA Carrier Targeting Cancer-Associated Fibroblasts Kuzmich, Alexey Rakitina, Olga Didych, Dmitry Potapov, Victor Zinovyeva, Marina Alekseenko, Irina Sverdlov, Eugene Polymers (Basel) Article Nuclear proteins, like histone H2A, are promising non-viral carriers for gene delivery since they are biocompatible, biodegradable, bear intrinsic nuclear localization signal, and are easy to modify. The addition of surface-protein-binding ligand to histone H2A may increase its DNA delivery efficiency. Tumor microenvironment (TME) is a promising target for gene therapy since its surface protein repertoire is more stable than that of cancer cells. Cancer-associated fibroblasts (CAFs) are important components of TME, and one of their surface markers is beta-type platelet-derived growth factor receptor (PDGFRβ). In this study, we fused histone H2A with PDGFRβ-binding peptide, YG2, to create a novel non-viral fibroblast-targeting DNA carrier, H2A-YG2. The transfection efficiency of histone complexes with pDNA encoding a bicistronic reporter (enhanced green fluorescent protein, EGFP, and firefly luciferase) in PDGFRβ-positive and PDGFRβ-negative cells was estimated by luciferase assay and flow cytometry. The luciferase activity, percentage of transfected cells, and overall EGFP fluorescence were increased due to histone modification with YG2 only in PDGFRβ-positive cells. We also estimated the internalization efficiency of DNA-carrier complexes using tetramethyl-rhodamine-labeled pDNA. The ligand fusion increased DNA internalization only in the PDGFRβ-positive cells. In conclusion, we demonstrated that the H2A-YG2 carrier targeted gene delivery to PDGFRβ-positive tumor stromal cells. MDPI 2020-07-29 /pmc/articles/PMC7464289/ /pubmed/32751200 http://dx.doi.org/10.3390/polym12081695 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Kuzmich, Alexey Rakitina, Olga Didych, Dmitry Potapov, Victor Zinovyeva, Marina Alekseenko, Irina Sverdlov, Eugene Novel Histone-Based DNA Carrier Targeting Cancer-Associated Fibroblasts |
title | Novel Histone-Based DNA Carrier Targeting Cancer-Associated Fibroblasts |
title_full | Novel Histone-Based DNA Carrier Targeting Cancer-Associated Fibroblasts |
title_fullStr | Novel Histone-Based DNA Carrier Targeting Cancer-Associated Fibroblasts |
title_full_unstemmed | Novel Histone-Based DNA Carrier Targeting Cancer-Associated Fibroblasts |
title_short | Novel Histone-Based DNA Carrier Targeting Cancer-Associated Fibroblasts |
title_sort | novel histone-based dna carrier targeting cancer-associated fibroblasts |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464289/ https://www.ncbi.nlm.nih.gov/pubmed/32751200 http://dx.doi.org/10.3390/polym12081695 |
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