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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...

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Autores principales: Han, Yaopin, Wu, Yixing, He, Binfeng, Wu, Di, Hua, Jianlan, Qian, Hang, Zhang, Jing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: RSC 2023
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.
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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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