Oral Piwi‐Interacting RNA Delivery Mediated by Green Tea‐Derived Exosome‐Like Nanovesicles for the Treatment of Aortic Dissection
Aortic dissection (AD) is a severe cardiovascular disease necessitating active therapeutic strategies for early intervention and prevention. Nucleic acid drugs, known for their potent molecule‐targeting therapeutic properties, offer potential for genetic suppression of AD. Piwi‐interacting RNAs, a c...
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| creator | Liu, Yan Qi, Hongzhao Zong, Jinbao Li, Min Yang, Yanyan Li, Xiaolu Li, Tianxiang Cho, Jae Youl Yu, Tao |
| description | Aortic dissection (AD) is a severe cardiovascular disease necessitating active therapeutic strategies for early intervention and prevention. Nucleic acid drugs, known for their potent molecule‐targeting therapeutic properties, offer potential for genetic suppression of AD. Piwi‐interacting RNAs, a class of small RNAs, hold promise for managing cardiovascular diseases. Limited research on these RNAs and AD exists. This study demonstrates that an antagomir targeting heart‐apoptosis‐associated piRNA (HAAPIR) effectively regulates vascular remodeling, mitigating AD occurrence and progression through the myocyte enhancer factor 2D (Mef2D) and matrix metallopeptidase 9 (MMP9) pathways. Green tea‐derived plant exosome‐like nanovesicles (PELNs) are used for oral administration of antagomir. The antagomir‐HAAPIR‐nanovesicle complex, after purification and optimization, exhibits a high packing rate, while the antagomir is resistant to enzyme digestion. Administered to mice, the complex targets the aortic lesion, reducing AD incidence and improving survival. Moreover, MMP9 and Mef2D expression decrease significantly, inhibiting the phenotypic conversion of human aortic smooth muscle cells. PELNs encapsulate the antagomir‐HAAPIR complex, maintaining stability, mediating transport into the bloodstream, and delivering Piwi‐interacting RNAs to AD sites. Thus, HAAPIR is a potential target for persistent clinical AD prevention and treatment, and nanovesicle‐encapsulated nucleic acids offer a promising cardiovascular disease treatment, providing insights for other therapeutic targets.
A novel anta‐HAAPIR delivery system based on green tea‐derived PELNs is developed in this study, which can realize effective oral delivery of anta‐HAAPIR for AD therapy, potentially promoting the development of oral nucleic acid drugs. |
| doi_str_mv | 10.1002/adhm.202401466 |
| format | Article |
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A novel anta‐HAAPIR delivery system based on green tea‐derived PELNs is developed in this study, which can realize effective oral delivery of anta‐HAAPIR for AD therapy, potentially promoting the development of oral nucleic acid drugs.</description><identifier>ISSN: 2192-2640</identifier><identifier>ISSN: 2192-2659</identifier><identifier>EISSN: 2192-2659</identifier><identifier>DOI: 10.1002/adhm.202401466</identifier><identifier>PMID: 39087398</identifier><language>eng</language><publisher>Germany: Wiley Subscription Services, Inc</publisher><subject>Administration, Oral ; Animals ; Aorta ; Aortic dissection ; Aortic Dissection - drug therapy ; Aortic Dissection - metabolism ; Aortic Dissection - therapy ; Apoptosis ; Cardiovascular disease ; Cardiovascular diseases ; Dissection ; Drug delivery ; Drug development ; Encapsulation ; Exosomes - chemistry ; Exosomes - metabolism ; Gelatinase B ; Genetic suppression ; Green tea ; Health services ; Heart diseases ; Humans ; Male ; Matrix Metalloproteinase 9 - metabolism ; Matrix metalloproteinases ; Metalloproteinase ; Mice ; Mice, Inbred C57BL ; MMP9 ; Myocytes ; Myocytes, Smooth Muscle - drug effects ; Myocytes, Smooth Muscle - metabolism ; Nanoparticles - chemistry ; Nucleic acids ; Oral administration ; oral delivery ; phenotypic conversion ; piRNA ; Piwi-Interacting RNA ; plant exosome‐like nanovesicles ; RNA, Small Interfering - chemistry ; Smooth muscle ; Tea - chemistry ; Therapeutic targets</subject><ispartof>Advanced healthcare materials, 2024-12, Vol.13 (30), p.e2401466-n/a</ispartof><rights>2024 Wiley‐VCH GmbH</rights><rights>2024 Wiley‐VCH GmbH.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c2986-ece382f121cf24da56703a1d03238a4182dcaa0d43622514a8ed3a623ffb6c253</cites><orcidid>0000-0002-0925-2242</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fadhm.202401466$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fadhm.202401466$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27903,27904,45553,45554</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39087398$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Liu, Yan</creatorcontrib><creatorcontrib>Qi, Hongzhao</creatorcontrib><creatorcontrib>Zong, Jinbao</creatorcontrib><creatorcontrib>Li, Min</creatorcontrib><creatorcontrib>Yang, Yanyan</creatorcontrib><creatorcontrib>Li, Xiaolu</creatorcontrib><creatorcontrib>Li, Tianxiang</creatorcontrib><creatorcontrib>Cho, Jae Youl</creatorcontrib><creatorcontrib>Yu, Tao</creatorcontrib><title>Oral Piwi‐Interacting RNA Delivery Mediated by Green Tea‐Derived Exosome‐Like Nanovesicles for the Treatment of Aortic Dissection</title><title>Advanced healthcare materials</title><addtitle>Adv Healthc Mater</addtitle><description>Aortic dissection (AD) is a severe cardiovascular disease necessitating active therapeutic strategies for early intervention and prevention. Nucleic acid drugs, known for their potent molecule‐targeting therapeutic properties, offer potential for genetic suppression of AD. Piwi‐interacting RNAs, a class of small RNAs, hold promise for managing cardiovascular diseases. Limited research on these RNAs and AD exists. This study demonstrates that an antagomir targeting heart‐apoptosis‐associated piRNA (HAAPIR) effectively regulates vascular remodeling, mitigating AD occurrence and progression through the myocyte enhancer factor 2D (Mef2D) and matrix metallopeptidase 9 (MMP9) pathways. Green tea‐derived plant exosome‐like nanovesicles (PELNs) are used for oral administration of antagomir. The antagomir‐HAAPIR‐nanovesicle complex, after purification and optimization, exhibits a high packing rate, while the antagomir is resistant to enzyme digestion. Administered to mice, the complex targets the aortic lesion, reducing AD incidence and improving survival. Moreover, MMP9 and Mef2D expression decrease significantly, inhibiting the phenotypic conversion of human aortic smooth muscle cells. PELNs encapsulate the antagomir‐HAAPIR complex, maintaining stability, mediating transport into the bloodstream, and delivering Piwi‐interacting RNAs to AD sites. Thus, HAAPIR is a potential target for persistent clinical AD prevention and treatment, and nanovesicle‐encapsulated nucleic acids offer a promising cardiovascular disease treatment, providing insights for other therapeutic targets.
A novel anta‐HAAPIR delivery system based on green tea‐derived PELNs is developed in this study, which can realize effective oral delivery of anta‐HAAPIR for AD therapy, potentially promoting the development of oral nucleic acid drugs.</description><subject>Administration, Oral</subject><subject>Animals</subject><subject>Aorta</subject><subject>Aortic dissection</subject><subject>Aortic Dissection - drug therapy</subject><subject>Aortic Dissection - metabolism</subject><subject>Aortic Dissection - therapy</subject><subject>Apoptosis</subject><subject>Cardiovascular disease</subject><subject>Cardiovascular diseases</subject><subject>Dissection</subject><subject>Drug delivery</subject><subject>Drug development</subject><subject>Encapsulation</subject><subject>Exosomes - chemistry</subject><subject>Exosomes - metabolism</subject><subject>Gelatinase B</subject><subject>Genetic suppression</subject><subject>Green tea</subject><subject>Health services</subject><subject>Heart diseases</subject><subject>Humans</subject><subject>Male</subject><subject>Matrix Metalloproteinase 9 - metabolism</subject><subject>Matrix metalloproteinases</subject><subject>Metalloproteinase</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>MMP9</subject><subject>Myocytes</subject><subject>Myocytes, Smooth Muscle - drug effects</subject><subject>Myocytes, Smooth Muscle - metabolism</subject><subject>Nanoparticles - chemistry</subject><subject>Nucleic acids</subject><subject>Oral administration</subject><subject>oral delivery</subject><subject>phenotypic conversion</subject><subject>piRNA</subject><subject>Piwi-Interacting RNA</subject><subject>plant exosome‐like nanovesicles</subject><subject>RNA, Small Interfering - chemistry</subject><subject>Smooth muscle</subject><subject>Tea - chemistry</subject><subject>Therapeutic targets</subject><issn>2192-2640</issn><issn>2192-2659</issn><issn>2192-2659</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1PGzEQhq2qqCDKlWNlqZdekvpj17GPEeFLClBV4WxN7Nliurum9gaaW2-99jfySzAKpFIvncuMRs_7zkgvIYecjTlj4jP4m24smKgYr5R6Q_YEN2IkVG3ebueK7ZKDnG9ZKVVzpfk7sisN0xNp9B75fZWgpV_CQ3j89ee8HzCBG0L_jX69nNIZtuEe05peoA8woKfLNT1NiD1dIBTBDFMBPD3-GXPssGzm4TvSS-jjPebgWsy0iYkON0gXCWHosB9obOg0piE4Ogs5Y7kX-_dkp4E248FL3yfXJ8eLo7PR_Or0_Gg6HzlhtBqhQ6lFwwV3jag81GrCJHDPpJAaKq6FdwDMV1IJUfMKNHoJSsimWSonarlPPm1871L8scI82C5kh20LPcZVtpJpZeqJ4bKgH_9Bb-Mq9eU7K7k0nMmJ1IUabyiXYs4JG3uXQgdpbTmzzynZ55TsNqUi-PBiu1p26Lf4ayYFMBvgIbS4_o-dnc7OLv6aPwF4BqDv</recordid><startdate>20241201</startdate><enddate>20241201</enddate><creator>Liu, Yan</creator><creator>Qi, Hongzhao</creator><creator>Zong, Jinbao</creator><creator>Li, Min</creator><creator>Yang, Yanyan</creator><creator>Li, Xiaolu</creator><creator>Li, Tianxiang</creator><creator>Cho, Jae Youl</creator><creator>Yu, Tao</creator><general>Wiley Subscription Services, Inc</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>7QF</scope><scope>7QP</scope><scope>7QQ</scope><scope>7SC</scope><scope>7SE</scope><scope>7SP</scope><scope>7SR</scope><scope>7T5</scope><scope>7TA</scope><scope>7TB</scope><scope>7TM</scope><scope>7TO</scope><scope>7U5</scope><scope>8BQ</scope><scope>8FD</scope><scope>F28</scope><scope>FR3</scope><scope>H8D</scope><scope>H8G</scope><scope>H94</scope><scope>JG9</scope><scope>JQ2</scope><scope>K9.</scope><scope>KR7</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-0925-2242</orcidid></search><sort><creationdate>20241201</creationdate><title>Oral Piwi‐Interacting RNA Delivery Mediated by Green Tea‐Derived Exosome‐Like Nanovesicles for the Treatment of Aortic Dissection</title><author>Liu, Yan ; Qi, Hongzhao ; Zong, Jinbao ; Li, Min ; Yang, Yanyan ; Li, Xiaolu ; Li, Tianxiang ; Cho, Jae Youl ; Yu, Tao</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c2986-ece382f121cf24da56703a1d03238a4182dcaa0d43622514a8ed3a623ffb6c253</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Administration, Oral</topic><topic>Animals</topic><topic>Aorta</topic><topic>Aortic dissection</topic><topic>Aortic Dissection - drug therapy</topic><topic>Aortic Dissection - metabolism</topic><topic>Aortic Dissection - therapy</topic><topic>Apoptosis</topic><topic>Cardiovascular disease</topic><topic>Cardiovascular diseases</topic><topic>Dissection</topic><topic>Drug delivery</topic><topic>Drug development</topic><topic>Encapsulation</topic><topic>Exosomes - chemistry</topic><topic>Exosomes - metabolism</topic><topic>Gelatinase B</topic><topic>Genetic suppression</topic><topic>Green tea</topic><topic>Health services</topic><topic>Heart diseases</topic><topic>Humans</topic><topic>Male</topic><topic>Matrix Metalloproteinase 9 - metabolism</topic><topic>Matrix metalloproteinases</topic><topic>Metalloproteinase</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>MMP9</topic><topic>Myocytes</topic><topic>Myocytes, Smooth Muscle - drug effects</topic><topic>Myocytes, Smooth Muscle - metabolism</topic><topic>Nanoparticles - chemistry</topic><topic>Nucleic acids</topic><topic>Oral administration</topic><topic>oral delivery</topic><topic>phenotypic conversion</topic><topic>piRNA</topic><topic>Piwi-Interacting RNA</topic><topic>plant exosome‐like nanovesicles</topic><topic>RNA, Small Interfering - chemistry</topic><topic>Smooth muscle</topic><topic>Tea - chemistry</topic><topic>Therapeutic targets</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Liu, Yan</creatorcontrib><creatorcontrib>Qi, Hongzhao</creatorcontrib><creatorcontrib>Zong, Jinbao</creatorcontrib><creatorcontrib>Li, Min</creatorcontrib><creatorcontrib>Yang, Yanyan</creatorcontrib><creatorcontrib>Li, Xiaolu</creatorcontrib><creatorcontrib>Li, Tianxiang</creatorcontrib><creatorcontrib>Cho, Jae Youl</creatorcontrib><creatorcontrib>Yu, Tao</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Aluminium Industry Abstracts</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Ceramic Abstracts</collection><collection>Computer and Information Systems Abstracts</collection><collection>Corrosion Abstracts</collection><collection>Electronics & Communications Abstracts</collection><collection>Engineered Materials Abstracts</collection><collection>Immunology Abstracts</collection><collection>Materials Business File</collection><collection>Mechanical & Transportation Engineering Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>ANTE: Abstracts in New Technology & Engineering</collection><collection>Engineering Research Database</collection><collection>Aerospace Database</collection><collection>Copper Technical Reference Library</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Materials Research Database</collection><collection>ProQuest Computer Science Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Civil Engineering Abstracts</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>Computer and Information Systems Abstracts Academic</collection><collection>Computer and Information Systems Abstracts Professional</collection><collection>MEDLINE - Academic</collection><jtitle>Advanced healthcare materials</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Liu, Yan</au><au>Qi, Hongzhao</au><au>Zong, Jinbao</au><au>Li, Min</au><au>Yang, Yanyan</au><au>Li, Xiaolu</au><au>Li, Tianxiang</au><au>Cho, Jae Youl</au><au>Yu, Tao</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Oral Piwi‐Interacting RNA Delivery Mediated by Green Tea‐Derived Exosome‐Like Nanovesicles for the Treatment of Aortic Dissection</atitle><jtitle>Advanced healthcare materials</jtitle><addtitle>Adv Healthc Mater</addtitle><date>2024-12-01</date><risdate>2024</risdate><volume>13</volume><issue>30</issue><spage>e2401466</spage><epage>n/a</epage><pages>e2401466-n/a</pages><issn>2192-2640</issn><issn>2192-2659</issn><eissn>2192-2659</eissn><abstract>Aortic dissection (AD) is a severe cardiovascular disease necessitating active therapeutic strategies for early intervention and prevention. Nucleic acid drugs, known for their potent molecule‐targeting therapeutic properties, offer potential for genetic suppression of AD. Piwi‐interacting RNAs, a class of small RNAs, hold promise for managing cardiovascular diseases. Limited research on these RNAs and AD exists. This study demonstrates that an antagomir targeting heart‐apoptosis‐associated piRNA (HAAPIR) effectively regulates vascular remodeling, mitigating AD occurrence and progression through the myocyte enhancer factor 2D (Mef2D) and matrix metallopeptidase 9 (MMP9) pathways. Green tea‐derived plant exosome‐like nanovesicles (PELNs) are used for oral administration of antagomir. The antagomir‐HAAPIR‐nanovesicle complex, after purification and optimization, exhibits a high packing rate, while the antagomir is resistant to enzyme digestion. Administered to mice, the complex targets the aortic lesion, reducing AD incidence and improving survival. Moreover, MMP9 and Mef2D expression decrease significantly, inhibiting the phenotypic conversion of human aortic smooth muscle cells. PELNs encapsulate the antagomir‐HAAPIR complex, maintaining stability, mediating transport into the bloodstream, and delivering Piwi‐interacting RNAs to AD sites. Thus, HAAPIR is a potential target for persistent clinical AD prevention and treatment, and nanovesicle‐encapsulated nucleic acids offer a promising cardiovascular disease treatment, providing insights for other therapeutic targets.
A novel anta‐HAAPIR delivery system based on green tea‐derived PELNs is developed in this study, which can realize effective oral delivery of anta‐HAAPIR for AD therapy, potentially promoting the development of oral nucleic acid drugs.</abstract><cop>Germany</cop><pub>Wiley Subscription Services, Inc</pub><pmid>39087398</pmid><doi>10.1002/adhm.202401466</doi><tpages>16</tpages><orcidid>https://orcid.org/0000-0002-0925-2242</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Administration, Oral Animals Aorta Aortic dissection Aortic Dissection - drug therapy Aortic Dissection - metabolism Aortic Dissection - therapy Apoptosis Cardiovascular disease Cardiovascular diseases Dissection Drug delivery Drug development Encapsulation Exosomes - chemistry Exosomes - metabolism Gelatinase B Genetic suppression Green tea Health services Heart diseases Humans Male Matrix Metalloproteinase 9 - metabolism Matrix metalloproteinases Metalloproteinase Mice Mice, Inbred C57BL MMP9 Myocytes Myocytes, Smooth Muscle - drug effects Myocytes, Smooth Muscle - metabolism Nanoparticles - chemistry Nucleic acids Oral administration oral delivery phenotypic conversion piRNA Piwi-Interacting RNA plant exosome‐like nanovesicles RNA, Small Interfering - chemistry Smooth muscle Tea - chemistry Therapeutic targets |
| title | Oral Piwi‐Interacting RNA Delivery Mediated by Green Tea‐Derived Exosome‐Like Nanovesicles for the Treatment of Aortic Dissection |
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