Co‐Polymer Carrier with Dual Advantages of Cartilage‐Penetrating and Targeting Improves Delivery and Efficacy of MicroRNA Treatment of Osteoarthritis
Osteoarthritis (OA) is a debilitating joint disease affecting nearly 400 million people with no efficient etiological therapies. OA is primarily identified by cartilage destruction, and gradual degeneration of the whole joint would happen when the OA progresses. Hence, cartilage has been identified...
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creator | Zhao, Yipu Deng, Xudong Tan, Shenxing Zhang, Jie Han, Jiangfan Wang, Xue Pei, Jiawei Li, Hui Deng, Xiaoni Yin, Chong Yin, Dachuan Tian, Ye Qian, Airong |
description | Osteoarthritis (OA) is a debilitating joint disease affecting nearly 400 million people with no efficient etiological therapies. OA is primarily identified by cartilage destruction, and gradual degeneration of the whole joint would happen when the OA progresses. Hence, cartilage has been identified as the primary therapeutic target of OA. Unfortunately, numerous barriers block the delivery of therapeutic agents into cartilage, including avascular traits and high hardness of the extracellular matrix. Herein, a cartilage‐targeting peptide (CAP) modified polyvinylamine (PVAm)‐ poly (lactic‐co‐glycolic acid) (PLGA) copolymer (CAP‐PVAm‐PLGA) is designed, which can form spherical nanoparticles with the r‐miR‐140 (CPP‐NPs). CPP‐NPs possessed enhanced mechanical properties due to the introduction of PLGA to vehicles. Meanwhile, CAP endowed the cartilage targeting which facilitated CPP‐NPs localization in cartilage. With such dual advantages, CPP‐NPs exhibited outstanding penetrability and accumulation in cartilage even subchondral bone, and can penetrate to a depth of 1000 µm into human cartilage. The degeneration area of cartilage is reduced by 65% and synovial inflammation score by 80% in OA mice, and the microarchitecture of subchondral bone is also ameliorated. These studies established a promising platform for therapeutic RNA delivery in OA therapy that overcame the cartilage barriers.
Co‐polymer nanoparticles (CPP‐NPs) are designed for improving RNA delivery for OA therapy with high penetrability and cartilage targeting advantages. PLGA modification brought higher penetration by enhancing mechanical properties, and CAP decoration further endowed the nanoparticle with cartilage targeting. CPP‐NPs overcome the biological barriers for anti‐arthrosis RNA delivery and thus hold superior OA therapy effects. |
doi_str_mv | 10.1002/adhm.202202143 |
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Co‐polymer nanoparticles (CPP‐NPs) are designed for improving RNA delivery for OA therapy with high penetrability and cartilage targeting advantages. PLGA modification brought higher penetration by enhancing mechanical properties, and CAP decoration further endowed the nanoparticle with cartilage targeting. CPP‐NPs overcome the biological barriers for anti‐arthrosis RNA delivery and thus hold superior OA therapy effects.</description><identifier>ISSN: 2192-2640</identifier><identifier>EISSN: 2192-2659</identifier><identifier>DOI: 10.1002/adhm.202202143</identifier><identifier>PMID: 36511367</identifier><language>eng</language><publisher>Germany: Wiley Subscription Services, Inc</publisher><subject>Animals ; Arthritis ; Cartilage ; Cartilage diseases ; cartilage targeting ; Cartilage, Articular ; Chemical compounds ; Computer architecture ; Copolymers ; co‐polymer nanoparticle ; Degeneration ; Extracellular matrix ; Glycolic acid ; Humans ; Joint diseases ; Joints (anatomy) ; Localization ; Mechanical properties ; Mice ; MicroRNAs ; miRNA ; Nanoparticles ; Osteoarthritis ; Osteoarthritis - drug therapy ; penetrability ; Peptides - therapeutic use ; Pharmacology ; Polylactide-co-glycolide ; Polymers - therapeutic use ; RNA delivery ; Subchondral bone ; Therapeutic targets</subject><ispartof>Advanced healthcare materials, 2023-01, Vol.12 (6), p.e2202143-n/a</ispartof><rights>2022 Wiley‐VCH GmbH</rights><rights>2022 Wiley-VCH GmbH.</rights><rights>2023 Wiley‐VCH GmbH</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3733-181b7500841396b815c138806c084f0e18a8d658842339efe3ef3780c560fb3</citedby><cites>FETCH-LOGICAL-c3733-181b7500841396b815c138806c084f0e18a8d658842339efe3ef3780c560fb3</cites><orcidid>0000-0002-0740-9218 ; 0000-0001-7053-5447 ; 0000-0002-4463-9581</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.202202143$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fadhm.202202143$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36511367$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhao, Yipu</creatorcontrib><creatorcontrib>Deng, Xudong</creatorcontrib><creatorcontrib>Tan, Shenxing</creatorcontrib><creatorcontrib>Zhang, Jie</creatorcontrib><creatorcontrib>Han, Jiangfan</creatorcontrib><creatorcontrib>Wang, Xue</creatorcontrib><creatorcontrib>Pei, Jiawei</creatorcontrib><creatorcontrib>Li, Hui</creatorcontrib><creatorcontrib>Deng, Xiaoni</creatorcontrib><creatorcontrib>Yin, Chong</creatorcontrib><creatorcontrib>Yin, Dachuan</creatorcontrib><creatorcontrib>Tian, Ye</creatorcontrib><creatorcontrib>Qian, Airong</creatorcontrib><title>Co‐Polymer Carrier with Dual Advantages of Cartilage‐Penetrating and Targeting Improves Delivery and Efficacy of MicroRNA Treatment of Osteoarthritis</title><title>Advanced healthcare materials</title><addtitle>Adv Healthc Mater</addtitle><description>Osteoarthritis (OA) is a debilitating joint disease affecting nearly 400 million people with no efficient etiological therapies. OA is primarily identified by cartilage destruction, and gradual degeneration of the whole joint would happen when the OA progresses. Hence, cartilage has been identified as the primary therapeutic target of OA. Unfortunately, numerous barriers block the delivery of therapeutic agents into cartilage, including avascular traits and high hardness of the extracellular matrix. Herein, a cartilage‐targeting peptide (CAP) modified polyvinylamine (PVAm)‐ poly (lactic‐co‐glycolic acid) (PLGA) copolymer (CAP‐PVAm‐PLGA) is designed, which can form spherical nanoparticles with the r‐miR‐140 (CPP‐NPs). CPP‐NPs possessed enhanced mechanical properties due to the introduction of PLGA to vehicles. Meanwhile, CAP endowed the cartilage targeting which facilitated CPP‐NPs localization in cartilage. With such dual advantages, CPP‐NPs exhibited outstanding penetrability and accumulation in cartilage even subchondral bone, and can penetrate to a depth of 1000 µm into human cartilage. The degeneration area of cartilage is reduced by 65% and synovial inflammation score by 80% in OA mice, and the microarchitecture of subchondral bone is also ameliorated. These studies established a promising platform for therapeutic RNA delivery in OA therapy that overcame the cartilage barriers.
Co‐polymer nanoparticles (CPP‐NPs) are designed for improving RNA delivery for OA therapy with high penetrability and cartilage targeting advantages. PLGA modification brought higher penetration by enhancing mechanical properties, and CAP decoration further endowed the nanoparticle with cartilage targeting. CPP‐NPs overcome the biological barriers for anti‐arthrosis RNA delivery and thus hold superior OA therapy effects.</description><subject>Animals</subject><subject>Arthritis</subject><subject>Cartilage</subject><subject>Cartilage diseases</subject><subject>cartilage targeting</subject><subject>Cartilage, Articular</subject><subject>Chemical compounds</subject><subject>Computer architecture</subject><subject>Copolymers</subject><subject>co‐polymer nanoparticle</subject><subject>Degeneration</subject><subject>Extracellular matrix</subject><subject>Glycolic acid</subject><subject>Humans</subject><subject>Joint diseases</subject><subject>Joints (anatomy)</subject><subject>Localization</subject><subject>Mechanical properties</subject><subject>Mice</subject><subject>MicroRNAs</subject><subject>miRNA</subject><subject>Nanoparticles</subject><subject>Osteoarthritis</subject><subject>Osteoarthritis - drug therapy</subject><subject>penetrability</subject><subject>Peptides - therapeutic use</subject><subject>Pharmacology</subject><subject>Polylactide-co-glycolide</subject><subject>Polymers - therapeutic use</subject><subject>RNA delivery</subject><subject>Subchondral bone</subject><subject>Therapeutic targets</subject><issn>2192-2640</issn><issn>2192-2659</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1OwzAMxyMEgmlw5YgqceGykTRNmx6nDdikwRDsXmWtswX1A5J0qDcegSuvx5OQbjAkLkSRbMc__-3ICJ0S3CcY-5ciWxV9H_vukoDuoY5PYr_nhyze3_kBPkInxjxhd0JGQk4O0RF1HqFh1EEfw-rz7f2-ypsCtDcUWitnX5VdeaNa5N4gW4vSiiUYr5Jt3qrcRW0NlGC1sKpceqLMvLnQS9hEk-JZV2tXMYJcrUE3m_yVlCoVadPq3KpUVw93A2-uQdgCStu-zoyFynVYaWWVOUYHUuQGTr5tFz1eX82H4950djMZDqa9lEaU9ggni4hhzANC43DBCUsJ5RyHqXuSGAgXPAsZ54FPaQwSKEgacZyyEMsF7aKLraob-aUGY5NCmRTyXJRQ1SbxIxbgIGaEOfT8D_pU1bp0sznKNaRRvKH6W8r90BgNMnnWqhC6SQhO2q0l7daS3dZcwdm3bL0oINvhPztyQLwFXlUOzT9yyWA0vv0V_wLNkaVR</recordid><startdate>20230101</startdate><enddate>20230101</enddate><creator>Zhao, Yipu</creator><creator>Deng, Xudong</creator><creator>Tan, Shenxing</creator><creator>Zhang, Jie</creator><creator>Han, Jiangfan</creator><creator>Wang, Xue</creator><creator>Pei, Jiawei</creator><creator>Li, Hui</creator><creator>Deng, Xiaoni</creator><creator>Yin, Chong</creator><creator>Yin, Dachuan</creator><creator>Tian, Ye</creator><creator>Qian, Airong</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/0000-0002-0740-9218</orcidid><orcidid>https://orcid.org/0000-0001-7053-5447</orcidid><orcidid>https://orcid.org/0000-0002-4463-9581</orcidid></search><sort><creationdate>20230101</creationdate><title>Co‐Polymer Carrier with Dual Advantages of Cartilage‐Penetrating and Targeting Improves Delivery and Efficacy of MicroRNA Treatment of Osteoarthritis</title><author>Zhao, Yipu ; Deng, Xudong ; Tan, Shenxing ; Zhang, Jie ; Han, Jiangfan ; Wang, Xue ; Pei, Jiawei ; Li, Hui ; Deng, Xiaoni ; Yin, Chong ; Yin, Dachuan ; Tian, Ye ; Qian, Airong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3733-181b7500841396b815c138806c084f0e18a8d658842339efe3ef3780c560fb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Animals</topic><topic>Arthritis</topic><topic>Cartilage</topic><topic>Cartilage diseases</topic><topic>cartilage targeting</topic><topic>Cartilage, Articular</topic><topic>Chemical compounds</topic><topic>Computer architecture</topic><topic>Copolymers</topic><topic>co‐polymer nanoparticle</topic><topic>Degeneration</topic><topic>Extracellular matrix</topic><topic>Glycolic acid</topic><topic>Humans</topic><topic>Joint diseases</topic><topic>Joints (anatomy)</topic><topic>Localization</topic><topic>Mechanical properties</topic><topic>Mice</topic><topic>MicroRNAs</topic><topic>miRNA</topic><topic>Nanoparticles</topic><topic>Osteoarthritis</topic><topic>Osteoarthritis - drug therapy</topic><topic>penetrability</topic><topic>Peptides - therapeutic use</topic><topic>Pharmacology</topic><topic>Polylactide-co-glycolide</topic><topic>Polymers - therapeutic use</topic><topic>RNA delivery</topic><topic>Subchondral bone</topic><topic>Therapeutic targets</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhao, Yipu</creatorcontrib><creatorcontrib>Deng, Xudong</creatorcontrib><creatorcontrib>Tan, Shenxing</creatorcontrib><creatorcontrib>Zhang, Jie</creatorcontrib><creatorcontrib>Han, Jiangfan</creatorcontrib><creatorcontrib>Wang, Xue</creatorcontrib><creatorcontrib>Pei, Jiawei</creatorcontrib><creatorcontrib>Li, Hui</creatorcontrib><creatorcontrib>Deng, Xiaoni</creatorcontrib><creatorcontrib>Yin, Chong</creatorcontrib><creatorcontrib>Yin, Dachuan</creatorcontrib><creatorcontrib>Tian, Ye</creatorcontrib><creatorcontrib>Qian, Airong</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>Zhao, Yipu</au><au>Deng, Xudong</au><au>Tan, Shenxing</au><au>Zhang, Jie</au><au>Han, Jiangfan</au><au>Wang, Xue</au><au>Pei, Jiawei</au><au>Li, Hui</au><au>Deng, Xiaoni</au><au>Yin, Chong</au><au>Yin, Dachuan</au><au>Tian, Ye</au><au>Qian, Airong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Co‐Polymer Carrier with Dual Advantages of Cartilage‐Penetrating and Targeting Improves Delivery and Efficacy of MicroRNA Treatment of Osteoarthritis</atitle><jtitle>Advanced healthcare materials</jtitle><addtitle>Adv Healthc Mater</addtitle><date>2023-01-01</date><risdate>2023</risdate><volume>12</volume><issue>6</issue><spage>e2202143</spage><epage>n/a</epage><pages>e2202143-n/a</pages><issn>2192-2640</issn><eissn>2192-2659</eissn><abstract>Osteoarthritis (OA) is a debilitating joint disease affecting nearly 400 million people with no efficient etiological therapies. OA is primarily identified by cartilage destruction, and gradual degeneration of the whole joint would happen when the OA progresses. Hence, cartilage has been identified as the primary therapeutic target of OA. Unfortunately, numerous barriers block the delivery of therapeutic agents into cartilage, including avascular traits and high hardness of the extracellular matrix. Herein, a cartilage‐targeting peptide (CAP) modified polyvinylamine (PVAm)‐ poly (lactic‐co‐glycolic acid) (PLGA) copolymer (CAP‐PVAm‐PLGA) is designed, which can form spherical nanoparticles with the r‐miR‐140 (CPP‐NPs). CPP‐NPs possessed enhanced mechanical properties due to the introduction of PLGA to vehicles. Meanwhile, CAP endowed the cartilage targeting which facilitated CPP‐NPs localization in cartilage. With such dual advantages, CPP‐NPs exhibited outstanding penetrability and accumulation in cartilage even subchondral bone, and can penetrate to a depth of 1000 µm into human cartilage. The degeneration area of cartilage is reduced by 65% and synovial inflammation score by 80% in OA mice, and the microarchitecture of subchondral bone is also ameliorated. These studies established a promising platform for therapeutic RNA delivery in OA therapy that overcame the cartilage barriers.
Co‐polymer nanoparticles (CPP‐NPs) are designed for improving RNA delivery for OA therapy with high penetrability and cartilage targeting advantages. PLGA modification brought higher penetration by enhancing mechanical properties, and CAP decoration further endowed the nanoparticle with cartilage targeting. CPP‐NPs overcome the biological barriers for anti‐arthrosis RNA delivery and thus hold superior OA therapy effects.</abstract><cop>Germany</cop><pub>Wiley Subscription Services, Inc</pub><pmid>36511367</pmid><doi>10.1002/adhm.202202143</doi><tpages>15</tpages><orcidid>https://orcid.org/0000-0002-0740-9218</orcidid><orcidid>https://orcid.org/0000-0001-7053-5447</orcidid><orcidid>https://orcid.org/0000-0002-4463-9581</orcidid></addata></record> |
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subjects | Animals Arthritis Cartilage Cartilage diseases cartilage targeting Cartilage, Articular Chemical compounds Computer architecture Copolymers co‐polymer nanoparticle Degeneration Extracellular matrix Glycolic acid Humans Joint diseases Joints (anatomy) Localization Mechanical properties Mice MicroRNAs miRNA Nanoparticles Osteoarthritis Osteoarthritis - drug therapy penetrability Peptides - therapeutic use Pharmacology Polylactide-co-glycolide Polymers - therapeutic use RNA delivery Subchondral bone Therapeutic targets |
title | Co‐Polymer Carrier with Dual Advantages of Cartilage‐Penetrating and Targeting Improves Delivery and Efficacy of MicroRNA Treatment of Osteoarthritis |
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