{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T16:35:31Z","timestamp":1783528531375,"version":"3.55.0"},"reference-count":89,"publisher":"Wiley","issue":"25","license":[{"start":{"date-parts":[[2025,8,9]],"date-time":"2025-08-09T00:00:00Z","timestamp":1754697600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003569","name":"Ministry of Food and Drug Safety","doi-asserted-by":"publisher","award":["PY0000026283"],"award-info":[{"award-number":["PY0000026283"]}],"id":[{"id":"10.13039\/501100003569","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Adv Healthcare Materials"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Liposomal membrane elasticity is a controlling parameter in designing liposome\u2010based drug delivery systems and significantly affects biodistribution and biofunctional effects. Although extensively investigated in tumor models, the impact of liposomal membrane elasticity on rheumatoid arthritis (RA) remains underexplored. RA presents unique challenges, such as tortuous blood vessels, increased permeability, and chronic inflammation, which necessitate a specialized drug delivery strategy. This study aims to address these challenges by developing an engineered mimicry of extracellular vesicles (EVs) that is based on a lipid\/polymer hybrid system incorporating poly(ethylene oxide)\u2010b\u2010poly(\u03b5\u2010caprolactone)\u2010b\u2010poly(ethylene oxide) (PEO\u2010<jats:italic>b<\/jats:italic>\u2010PCL\u2010<jats:italic>b<\/jats:italic>\u2010PEO) to improve mechanical robustness and therapeutic performance.Tri\u2010ARTEX is developed as a lipid\/polymer hybrid liposome encapsulating stem cell extract (CE) and microRNA (AntagomiR155), and tuned its membrane elasticity by varying the PEO\u2010<jats:italic>b<\/jats:italic>\u2010PCL\u2010<jats:italic>b<\/jats:italic>\u2010PEO fraction. Tri\u2010ARTEX exhibited enhanced cellular uptake in Raw 264.7 macrophages as the PEO\u2010b\u2010PCL\u2010b\u2010PEO fraction increases. However, semi\u2010elastic Tri\u2010ARTEX<jats:sub>8:2<\/jats:sub> showed distinct biodistribution profiles and therapeutic effects in a murine collagen\u2010induced arthritis (CIA) model. Compared to its soft and rigid counterparts, semi\u2010elastic Tri\u2010ARTEX<jats:sub>8:2<\/jats:sub> improved blood circulation, targeted accumulation in inflamed joints, and anti\u2010inflammatory efficacy. Our findings suggest that these mechanobiologically engineered liposomal EV mimics with regulated membrane elasticity provide new capabilities for designing drug nanocarriers for targeted RA therapy and help to address the unique pathophysiological challenges of RA.<\/jats:p>","DOI":"10.1002\/adhm.202500795","type":"journal-article","created":{"date-parts":[[2025,8,9]],"date-time":"2025-08-09T11:25:31Z","timestamp":1754738731000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Mechanobiologically Engineered Mimicry of Extracellular Vesicles for Improved Systemic Biodistribution and Anti\u2010Inflammatory Treatment Efficacy in Rheumatoid Arthritis"],"prefix":"10.1002","volume":"14","author":[{"given":"Dahwun","family":"Kim","sequence":"first","affiliation":[{"name":"School of Pharmacy Sungkyunkwan University  Suwon 16149 Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hwira","family":"Baek","sequence":"additional","affiliation":[{"name":"School of Chemical Engineering Sungkyunkwan University  Suwon 16149 Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su Yeon","family":"Lim","sequence":"additional","affiliation":[{"name":"School of Pharmacy Sungkyunkwan University  Suwon 16149 Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min Sang","family":"Lee","sequence":"additional","affiliation":[{"name":"School of Pharmacy Sungkyunkwan University  Suwon 16149 Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyan","family":"Lyu","sequence":"additional","affiliation":[{"name":"School of Pharmacy Sungkyunkwan University  Suwon 16149 Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jihyun","family":"Lee","sequence":"additional","affiliation":[{"name":"School of Pharmacy Sungkyunkwan University  Suwon 16149 Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tun Naw","family":"Sut","sequence":"additional","affiliation":[{"name":"School of Chemical Engineering Sungkyunkwan University  Suwon 16149 Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"School of Chemical Engineering Sungkyunkwan University  Suwon 16149 Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeong Yi","family":"Kang","sequence":"additional","affiliation":[{"name":"School of Chemical Engineering Sungkyunkwan University  Suwon 16149 Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua A.","family":"Jackman","sequence":"additional","affiliation":[{"name":"School of Chemical Engineering Sungkyunkwan University  Suwon 16149 Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin Woong","family":"Kim","sequence":"additional","affiliation":[{"name":"School of Chemical Engineering Sungkyunkwan University  Suwon 16149 Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4836-3551","authenticated-orcid":false,"given":"Ji Hoon","family":"Jeong","sequence":"additional","affiliation":[{"name":"School of Pharmacy Sungkyunkwan University  Suwon 16149 Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,9]]},"reference":[{"key":"e_1_2_10_1_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01661"},{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1004965"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2015.95"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)60784-3"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.42036"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/mp2000742"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2022.113126"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.2217\/nnm.15.45"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/nano8010042"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.4161\/tisb.29528"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-02588-9"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2020.07.010"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-020-00675-6"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2020.10.069"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abe0083"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10787-022-01100-0"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/stem.2575"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aau6977"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/burnst\/tkae062"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-022-00959-4"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-021-01219-2"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10787-022-01115-7"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1517\/17425247.2.3.465"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics10020057"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajps.2014.09.004"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2021.05.010"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2014.06.046"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1010013108"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1021\/nn301159a"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.5b00147"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.5b04866"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.molpharmaceut.7b00051"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcis.2019.10.109"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2019.05.014"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jpcb.5b02891"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2020.12.014"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41578-021-00358-0"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.146.12.4234"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2006.03.039"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2011.07.028"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2022.120574"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2020.01.049"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.3390\/pr11061718"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0005-2736(97)00066-7"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.1c04996"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.8b22693"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.msec.2014.06.003"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.progpolymsci.2010.04.002"},{"key":"e_1_2_10_49_1","volume-title":"Piezoelectric Sensors","author":"Jackman J. A.","year":"2024"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.6b02532"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1021\/la904743d"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1063\/1.3687351"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.macromol.6b01164"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-019-0583-3"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1039\/C6CS00636A"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines10071725"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.21072"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1019536108"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1111\/1756-185X.13202"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-023-03523-0"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01704-0"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1039\/D2NH00070A"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.0c02006"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-022-01660-x"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2021.112586"},{"key":"e_1_2_10_66_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.9b01181"},{"key":"e_1_2_10_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.01.043"},{"key":"e_1_2_10_68_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.11108"},{"key":"e_1_2_10_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-5173(02)00129-1"},{"key":"e_1_2_10_70_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-17360-9"},{"key":"e_1_2_10_71_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gt.3300390"},{"key":"e_1_2_10_72_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdr300"},{"key":"e_1_2_10_73_1","doi-asserted-by":"publisher","DOI":"10.1002\/hed.23397"},{"key":"e_1_2_10_74_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2015.02.003"},{"key":"e_1_2_10_75_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0154009"},{"key":"e_1_2_10_76_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdu025"},{"key":"e_1_2_10_77_1","doi-asserted-by":"publisher","DOI":"10.1021\/la0602261"},{"key":"e_1_2_10_78_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsmacrolett.5b00743"},{"key":"e_1_2_10_79_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.macromol.6b02580"},{"key":"e_1_2_10_80_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.polymertesting.2016.11.018"},{"key":"e_1_2_10_81_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2019.02.010"},{"key":"e_1_2_10_82_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-05061-3"},{"key":"e_1_2_10_83_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.langmuir.6b00741"},{"key":"e_1_2_10_84_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.langmuir.8b01121"},{"key":"e_1_2_10_85_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.langmuir.0c00262"},{"key":"e_1_2_10_86_1","doi-asserted-by":"publisher","DOI":"10.1021\/la503203a"},{"key":"e_1_2_10_87_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.langmuir.1c00687"},{"key":"e_1_2_10_88_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.mie.2020.04.018"},{"key":"e_1_2_10_89_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2007.173"}],"container-title":["Advanced Healthcare Materials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adhm.202500795","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T08:47:14Z","timestamp":1759135634000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/adhm.202500795"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,9]]},"references-count":89,"journal-issue":{"issue":"25","published-print":{"date-parts":[[2025,9]]}},"alternative-id":["10.1002\/adhm.202500795"],"URL":"https:\/\/doi.org\/10.1002\/adhm.202500795","archive":["Portico"],"relation":{},"ISSN":["2192-2640","2192-2659"],"issn-type":[{"value":"2192-2640","type":"print"},{"value":"2192-2659","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,9]]},"assertion":[{"value":"2025-02-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2500795"}}