Nebulized Inhalation of Peptide-Modified DNA Origami To Alleviate Acute Lung Injury
Acute lung injury (ALI) is a severe inflammatory lung disease, with high mortality rates. Early intervention by reactive oxygen species (ROS) scavengers could reduce ROS accumulation, break the inflammation expansion chain in alveolar macrophages (AMs), and avoid irreversible damage to alveolar epit...
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Veröffentlicht in: | Nano letters 2024-05, Vol.24 (20), p.6102-6111 |
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creator | Wang, Haiyan Jiao, Yunfei Ma, Shuaijing Li, Zhuoting Gong, Jintao Jiang, Qiao Shang, Yingxu Li, Hongling Li, Jing Li, Na Zhao, Robert Chunhua Ding, Baoquan |
description | Acute lung injury (ALI) is a severe inflammatory lung disease, with high mortality rates. Early intervention by reactive oxygen species (ROS) scavengers could reduce ROS accumulation, break the inflammation expansion chain in alveolar macrophages (AMs), and avoid irreversible damage to alveolar epithelial and endothelial cells. Here, we reported cell-penetrating R9 peptide-modified triangular DNA origami nanostructures (tDONs-R9) as a novel nebulizable drug that could reach the deep alveolar regions and exhibit an enhanced uptake preference of macrophages. tDONs-R9 suppressed the expression of pro-inflammatory cytokines and drove polarization toward the anti-inflammatory M2 phenotype in macrophages. In the LPS-induced ALI mouse model, treatment with nebulized tDONs-R9 alleviated the overwhelming ROS, pro-inflammatory cytokines, and neutrophil infiltration in the lungs. Our study demonstrates that tDONs-R9 has the potential for ALI treatment, and the programmable DNA origami nanostructures provide a new drug delivery platform for pulmonary disease treatment with high delivery efficiency and biosecurity. |
doi_str_mv | 10.1021/acs.nanolett.4c01222 |
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Early intervention by reactive oxygen species (ROS) scavengers could reduce ROS accumulation, break the inflammation expansion chain in alveolar macrophages (AMs), and avoid irreversible damage to alveolar epithelial and endothelial cells. Here, we reported cell-penetrating R9 peptide-modified triangular DNA origami nanostructures (tDONs-R9) as a novel nebulizable drug that could reach the deep alveolar regions and exhibit an enhanced uptake preference of macrophages. tDONs-R9 suppressed the expression of pro-inflammatory cytokines and drove polarization toward the anti-inflammatory M2 phenotype in macrophages. In the LPS-induced ALI mouse model, treatment with nebulized tDONs-R9 alleviated the overwhelming ROS, pro-inflammatory cytokines, and neutrophil infiltration in the lungs. Our study demonstrates that tDONs-R9 has the potential for ALI treatment, and the programmable DNA origami nanostructures provide a new drug delivery platform for pulmonary disease treatment with high delivery efficiency and biosecurity.</description><identifier>ISSN: 1530-6984</identifier><identifier>EISSN: 1530-6992</identifier><identifier>DOI: 10.1021/acs.nanolett.4c01222</identifier><identifier>PMID: 38739578</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Acute Lung Injury - chemically induced ; Acute Lung Injury - drug therapy ; Acute Lung Injury - pathology ; Administration, Inhalation ; Animals ; Cell-Penetrating Peptides - chemistry ; Cytokines - metabolism ; Disease Models, Animal ; DNA - chemistry ; Drug Delivery Systems ; Lipopolysaccharides ; Macrophages, Alveolar - drug effects ; Macrophages, Alveolar - metabolism ; Mice ; Nanostructures - chemistry ; Nebulizers and Vaporizers ; Peptides - chemistry ; RAW 264.7 Cells ; Reactive Oxygen Species - metabolism</subject><ispartof>Nano letters, 2024-05, Vol.24 (20), p.6102-6111</ispartof><rights>2024 American Chemical Society</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-a297t-cda33fc40acdd75effb580a0807875ba28ccbc2790399f0351ef9f95c29fabff3</cites><orcidid>0000-0003-1095-8872 ; 0000-0002-2587-6944</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/acs.nanolett.4c01222$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/acs.nanolett.4c01222$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,776,780,2752,27053,27901,27902,56713,56763</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38739578$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Haiyan</creatorcontrib><creatorcontrib>Jiao, Yunfei</creatorcontrib><creatorcontrib>Ma, Shuaijing</creatorcontrib><creatorcontrib>Li, Zhuoting</creatorcontrib><creatorcontrib>Gong, Jintao</creatorcontrib><creatorcontrib>Jiang, Qiao</creatorcontrib><creatorcontrib>Shang, Yingxu</creatorcontrib><creatorcontrib>Li, Hongling</creatorcontrib><creatorcontrib>Li, Jing</creatorcontrib><creatorcontrib>Li, Na</creatorcontrib><creatorcontrib>Zhao, Robert Chunhua</creatorcontrib><creatorcontrib>Ding, Baoquan</creatorcontrib><title>Nebulized Inhalation of Peptide-Modified DNA Origami To Alleviate Acute Lung Injury</title><title>Nano letters</title><addtitle>Nano Lett</addtitle><description>Acute lung injury (ALI) is a severe inflammatory lung disease, with high mortality rates. Early intervention by reactive oxygen species (ROS) scavengers could reduce ROS accumulation, break the inflammation expansion chain in alveolar macrophages (AMs), and avoid irreversible damage to alveolar epithelial and endothelial cells. Here, we reported cell-penetrating R9 peptide-modified triangular DNA origami nanostructures (tDONs-R9) as a novel nebulizable drug that could reach the deep alveolar regions and exhibit an enhanced uptake preference of macrophages. tDONs-R9 suppressed the expression of pro-inflammatory cytokines and drove polarization toward the anti-inflammatory M2 phenotype in macrophages. In the LPS-induced ALI mouse model, treatment with nebulized tDONs-R9 alleviated the overwhelming ROS, pro-inflammatory cytokines, and neutrophil infiltration in the lungs. Our study demonstrates that tDONs-R9 has the potential for ALI treatment, and the programmable DNA origami nanostructures provide a new drug delivery platform for pulmonary disease treatment with high delivery efficiency and biosecurity.</description><subject>Acute Lung Injury - chemically induced</subject><subject>Acute Lung Injury - drug therapy</subject><subject>Acute Lung Injury - pathology</subject><subject>Administration, Inhalation</subject><subject>Animals</subject><subject>Cell-Penetrating Peptides - chemistry</subject><subject>Cytokines - metabolism</subject><subject>Disease Models, Animal</subject><subject>DNA - chemistry</subject><subject>Drug Delivery Systems</subject><subject>Lipopolysaccharides</subject><subject>Macrophages, Alveolar - drug effects</subject><subject>Macrophages, Alveolar - metabolism</subject><subject>Mice</subject><subject>Nanostructures - chemistry</subject><subject>Nebulizers and Vaporizers</subject><subject>Peptides - chemistry</subject><subject>RAW 264.7 Cells</subject><subject>Reactive Oxygen Species - metabolism</subject><issn>1530-6984</issn><issn>1530-6992</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kMtOwzAQRS0EolD4A4SyZJMysWNiL6PyqlRaJMo6chy7uEriYidI5etx1ceSzcxIc-8dzUHoJoFRAji5F9KPWtHaWnXdKJWQYIxP0EVCCcQPnOPT48zSAbr0fgUAnFA4RwPCMsJpxi7Qx0yVfW1-VRVN2i9Ri87YNrI6elfrzlQqfrOV0SasH2d5NHdmKRoTLWyU17X6MaJTUS77UKd9uwwRq95trtCZFrVX1_s-RJ_PT4vxazydv0zG-TQWmGddLCtBiJYpCFlVGVVal5SBAAYZy2gpMJOylDjjQDjXQGiiNNecSsy1KLUmQ3S3y107-90r3xWN8VLVtWiV7X1BgKaM8IzxIE13Uums907pYu1MI9ymSKDY4iwCzuKAs9jjDLbb_YW-bFR1NB34BQHsBFv7yvauDQ__n_kHXNeFUA</recordid><startdate>20240522</startdate><enddate>20240522</enddate><creator>Wang, Haiyan</creator><creator>Jiao, Yunfei</creator><creator>Ma, Shuaijing</creator><creator>Li, Zhuoting</creator><creator>Gong, Jintao</creator><creator>Jiang, Qiao</creator><creator>Shang, Yingxu</creator><creator>Li, Hongling</creator><creator>Li, Jing</creator><creator>Li, Na</creator><creator>Zhao, Robert Chunhua</creator><creator>Ding, Baoquan</creator><general>American Chemical Society</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-1095-8872</orcidid><orcidid>https://orcid.org/0000-0002-2587-6944</orcidid></search><sort><creationdate>20240522</creationdate><title>Nebulized Inhalation of Peptide-Modified DNA Origami To Alleviate Acute Lung Injury</title><author>Wang, Haiyan ; Jiao, Yunfei ; Ma, Shuaijing ; Li, Zhuoting ; Gong, Jintao ; Jiang, Qiao ; Shang, Yingxu ; Li, Hongling ; Li, Jing ; Li, Na ; Zhao, Robert Chunhua ; Ding, Baoquan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a297t-cda33fc40acdd75effb580a0807875ba28ccbc2790399f0351ef9f95c29fabff3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Acute Lung Injury - chemically induced</topic><topic>Acute Lung Injury - drug therapy</topic><topic>Acute Lung Injury - pathology</topic><topic>Administration, Inhalation</topic><topic>Animals</topic><topic>Cell-Penetrating Peptides - chemistry</topic><topic>Cytokines - metabolism</topic><topic>Disease Models, Animal</topic><topic>DNA - chemistry</topic><topic>Drug Delivery Systems</topic><topic>Lipopolysaccharides</topic><topic>Macrophages, Alveolar - drug effects</topic><topic>Macrophages, Alveolar - metabolism</topic><topic>Mice</topic><topic>Nanostructures - chemistry</topic><topic>Nebulizers and Vaporizers</topic><topic>Peptides - chemistry</topic><topic>RAW 264.7 Cells</topic><topic>Reactive Oxygen Species - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Haiyan</creatorcontrib><creatorcontrib>Jiao, Yunfei</creatorcontrib><creatorcontrib>Ma, Shuaijing</creatorcontrib><creatorcontrib>Li, Zhuoting</creatorcontrib><creatorcontrib>Gong, Jintao</creatorcontrib><creatorcontrib>Jiang, Qiao</creatorcontrib><creatorcontrib>Shang, Yingxu</creatorcontrib><creatorcontrib>Li, Hongling</creatorcontrib><creatorcontrib>Li, Jing</creatorcontrib><creatorcontrib>Li, Na</creatorcontrib><creatorcontrib>Zhao, Robert Chunhua</creatorcontrib><creatorcontrib>Ding, Baoquan</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Nano letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Haiyan</au><au>Jiao, Yunfei</au><au>Ma, Shuaijing</au><au>Li, Zhuoting</au><au>Gong, Jintao</au><au>Jiang, Qiao</au><au>Shang, Yingxu</au><au>Li, Hongling</au><au>Li, Jing</au><au>Li, Na</au><au>Zhao, Robert Chunhua</au><au>Ding, Baoquan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Nebulized Inhalation of Peptide-Modified DNA Origami To Alleviate Acute Lung Injury</atitle><jtitle>Nano letters</jtitle><addtitle>Nano Lett</addtitle><date>2024-05-22</date><risdate>2024</risdate><volume>24</volume><issue>20</issue><spage>6102</spage><epage>6111</epage><pages>6102-6111</pages><issn>1530-6984</issn><eissn>1530-6992</eissn><abstract>Acute lung injury (ALI) is a severe inflammatory lung disease, with high mortality rates. Early intervention by reactive oxygen species (ROS) scavengers could reduce ROS accumulation, break the inflammation expansion chain in alveolar macrophages (AMs), and avoid irreversible damage to alveolar epithelial and endothelial cells. Here, we reported cell-penetrating R9 peptide-modified triangular DNA origami nanostructures (tDONs-R9) as a novel nebulizable drug that could reach the deep alveolar regions and exhibit an enhanced uptake preference of macrophages. tDONs-R9 suppressed the expression of pro-inflammatory cytokines and drove polarization toward the anti-inflammatory M2 phenotype in macrophages. In the LPS-induced ALI mouse model, treatment with nebulized tDONs-R9 alleviated the overwhelming ROS, pro-inflammatory cytokines, and neutrophil infiltration in the lungs. Our study demonstrates that tDONs-R9 has the potential for ALI treatment, and the programmable DNA origami nanostructures provide a new drug delivery platform for pulmonary disease treatment with high delivery efficiency and biosecurity.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>38739578</pmid><doi>10.1021/acs.nanolett.4c01222</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0003-1095-8872</orcidid><orcidid>https://orcid.org/0000-0002-2587-6944</orcidid></addata></record> |
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subjects | Acute Lung Injury - chemically induced Acute Lung Injury - drug therapy Acute Lung Injury - pathology Administration, Inhalation Animals Cell-Penetrating Peptides - chemistry Cytokines - metabolism Disease Models, Animal DNA - chemistry Drug Delivery Systems Lipopolysaccharides Macrophages, Alveolar - drug effects Macrophages, Alveolar - metabolism Mice Nanostructures - chemistry Nebulizers and Vaporizers Peptides - chemistry RAW 264.7 Cells Reactive Oxygen Species - metabolism |
title | Nebulized Inhalation of Peptide-Modified DNA Origami To Alleviate Acute Lung Injury |
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