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DNA nanoparticles targeting FOXO4 selectively eliminate cigarette smoke-induced senescent lung fibroblasts
The pathogenesis and development of chronic obstructive pulmonary disease (COPD) are significantly related to cellular senescence. Strategies to eliminate senescent cells have been confirmed to benefit several senescence-related diseases. However, there are few reports of senolytic drugs in COPD man...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
RSC
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10597553/ https://www.ncbi.nlm.nih.gov/pubmed/37881696 http://dx.doi.org/10.1039/d3na00547j |
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author | Han, Yaopin Wu, Yixing He, Binfeng Wu, Di Hua, Jianlan Qian, Hang Zhang, Jing |
author_facet | Han, Yaopin Wu, Yixing He, Binfeng Wu, Di Hua, Jianlan Qian, Hang Zhang, Jing |
author_sort | Han, Yaopin |
collection | PubMed |
description | The pathogenesis and development of chronic obstructive pulmonary disease (COPD) are significantly related to cellular senescence. Strategies to eliminate senescent cells have been confirmed to benefit several senescence-related diseases. However, there are few reports of senolytic drugs in COPD management. In this study, we demonstrated elevated FOXO4 expression in cigarette smoke-induced senescent lung fibroblasts both in vitro and in vivo. Additionally, self-assembled DNA nanotubes loaded with single-stranded FOXO4 siRNA (siFOXO4-NT) were designed and synthesized to knockdown FOXO4 in senescent fibroblasts. We found that siFOXO4-NT can concentration- and time-dependently enter human lung fibroblasts (HFL-1 cells), thereby reducing FOXO4 levels in vitro. Most importantly, siFOXO4-NT selectively cleared senescent HFL-1 cells by reducing BCLXL expression and the BCL2/BAX ratio, which were increased in CSE-induced senescent HFL-1 cells. The findings from our work present a novel strategy for senolytic drug development for COPD therapy. |
format | Online Article Text |
id | pubmed-10597553 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | RSC |
record_format | MEDLINE/PubMed |
spelling | pubmed-105975532023-10-25 DNA nanoparticles targeting FOXO4 selectively eliminate cigarette smoke-induced senescent lung fibroblasts Han, Yaopin Wu, Yixing He, Binfeng Wu, Di Hua, Jianlan Qian, Hang Zhang, Jing Nanoscale Adv Chemistry The pathogenesis and development of chronic obstructive pulmonary disease (COPD) are significantly related to cellular senescence. Strategies to eliminate senescent cells have been confirmed to benefit several senescence-related diseases. However, there are few reports of senolytic drugs in COPD management. In this study, we demonstrated elevated FOXO4 expression in cigarette smoke-induced senescent lung fibroblasts both in vitro and in vivo. Additionally, self-assembled DNA nanotubes loaded with single-stranded FOXO4 siRNA (siFOXO4-NT) were designed and synthesized to knockdown FOXO4 in senescent fibroblasts. We found that siFOXO4-NT can concentration- and time-dependently enter human lung fibroblasts (HFL-1 cells), thereby reducing FOXO4 levels in vitro. Most importantly, siFOXO4-NT selectively cleared senescent HFL-1 cells by reducing BCLXL expression and the BCL2/BAX ratio, which were increased in CSE-induced senescent HFL-1 cells. The findings from our work present a novel strategy for senolytic drug development for COPD therapy. RSC 2023-10-05 /pmc/articles/PMC10597553/ /pubmed/37881696 http://dx.doi.org/10.1039/d3na00547j Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by-nc/3.0/ |
spellingShingle | Chemistry Han, Yaopin Wu, Yixing He, Binfeng Wu, Di Hua, Jianlan Qian, Hang Zhang, Jing DNA nanoparticles targeting FOXO4 selectively eliminate cigarette smoke-induced senescent lung fibroblasts |
title | DNA nanoparticles targeting FOXO4 selectively eliminate cigarette smoke-induced senescent lung fibroblasts |
title_full | DNA nanoparticles targeting FOXO4 selectively eliminate cigarette smoke-induced senescent lung fibroblasts |
title_fullStr | DNA nanoparticles targeting FOXO4 selectively eliminate cigarette smoke-induced senescent lung fibroblasts |
title_full_unstemmed | DNA nanoparticles targeting FOXO4 selectively eliminate cigarette smoke-induced senescent lung fibroblasts |
title_short | DNA nanoparticles targeting FOXO4 selectively eliminate cigarette smoke-induced senescent lung fibroblasts |
title_sort | dna nanoparticles targeting foxo4 selectively eliminate cigarette smoke-induced senescent lung fibroblasts |
topic | Chemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10597553/ https://www.ncbi.nlm.nih.gov/pubmed/37881696 http://dx.doi.org/10.1039/d3na00547j |
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