{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T16:55:06Z","timestamp":1791824106732,"version":"4.3.4"},"reference-count":53,"publisher":"Wiley","issue":"30","license":[{"start":{"date-parts":[[2024,8,18]],"date-time":"2024-08-18T00:00:00Z","timestamp":1723939200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Adv Healthcare Materials"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Pulmonary hypertension (PH) is a life\u2010threatening cardiovascular disease with a lack of effective treatment options. Nanozymes, though promising for PH therapy, pose safety risks due to their metallic nature. Here, a non\u2010metallic nanozyme is reported for the treatment of monocrotaline (MCT)\u2010induced PH with a therapeutic mechanism involving the ROS\/TGF\u2010\u03b21 signaling. The synthesized melanin\u2010polyvinylpyrrolidone\u2010polyethylene glycol (MPP) nanoparticles showcase\u00a0ultra\u2010small size, excellent water solubility, high biocompatibility, and remarkable antioxidant capacity. The MPP nanoparticles are capable of effectively eliminating ROS in isolated pulmonary artery smooth muscle cells (PASMCs) from PH rats, and significantly reduce\u00a0PASMC proliferation and migration. In vivo results from a PH model demonstrate\u00a0that MPP nanoparticles significantly increase\u00a0pulmonary artery acceleration time, decrease\u00a0wall thickening and PCNA expression in lung tissues, as evidenced by echocardiograpy, histology and immunoblot analysis. Additionally, MPP nanoparticles treatment improve\u00a0running capacity, decrease\u00a0Fulton index, and attenuate\u00a0right ventricular fibrosis in MCT\u2010PH rats by using treadmill test, picrosirius red, and trichrome Masson staining. Further transcriptomic and biochemical analyses reveal\u00a0that inhibiting ROS\u2010driven activation of TGF\u2010\u03b21 in the PA is the mechanism by which MPP nanoparticles exert\u00a0their therapeutic effect. This study provides\u00a0a novel approach for treating PH with non\u2010metallic nanozymes based on a well\u2010understood mechanism.<\/jats:p>","DOI":"10.1002\/adhm.202401909","type":"journal-article","created":{"date-parts":[[2024,8,19]],"date-time":"2024-08-19T00:08:05Z","timestamp":1724026085000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["A Non\u2010Metallic Nanozyme Ameliorates Pulmonary Hypertension Through Inhibiting ROS\/TGF\u2010\u03b21 Signaling"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0801-8435","authenticated-orcid":false,"given":"Ruxia","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Rehabilitation School of Medical Technology Tianjin Medical University  Tianjin 300203 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Medical Imaging Tianjin Medical University  Tianjin 300203 China"},{"name":"Department of CT Shaanxi Provincial People's Hospital  Xi'an Shaanxi Province 710068 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinsheng","family":"Li","sequence":"additional","affiliation":[{"name":"School of Medical Imaging Tianjin Medical University  Tianjin 300203 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quan","family":"Zou","sequence":"additional","affiliation":[{"name":"School of Medical Imaging Tianjin Key Laboratory of Functional Imaging Tianjin Medical University  Tianjin 300203 China"},{"name":"Department of Radiology The Second Hospital of Tianjin Medical University  Tianjin 300211 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaojiao","family":"Yu","sequence":"additional","affiliation":[{"name":"School of Medical Imaging Tianjin Medical University  Tianjin 300203 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Ye","sequence":"additional","affiliation":[{"name":"Trauma Treatment Center Peking University People's Hospital Key Laboratory of Trauma Treatment and Neural Regeneration (Peking University) Ministry of Education National Center for Trauma Medicine  Beijing 100044 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhui","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology The Second Hospital of Tianjin Medical University  Tianjin 300211 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Ultrasound Tianjin Third Central Hospital  Tianjin 300170 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6136-9969","authenticated-orcid":false,"given":"Shao\u2010Kai","family":"Sun","sequence":"additional","affiliation":[{"name":"School of Medical Imaging Tianjin Medical University  Tianjin 300203 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,8,18]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells13030244"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-023-01535-6"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.123.067579"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2023.07.006"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2022-0360OC"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2022.12.012"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(15)00543-3"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01668-1"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2023.11.012"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.202009-3698OC"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-023-04361-7"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox12122060"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvx234"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01324.2007"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2024.103049"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000127950.13380.FD"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.08.001"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200707-1083OC"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01857-2017"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-018-0068-3"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2009.080565"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells11182795"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2024.e27539"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2021.07.010"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1039\/C8CS00457A"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202301232"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2018.07.049"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2023.215245"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2022.214784"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202300252"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2014.08.037"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-022-01295-y"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.202110432"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.2c06981"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.8b04022"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/smll.202207350"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.201904833"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.201903129"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.201204683"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1021\/bm101281b"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2024.02.021"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202303101"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2023.122231"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1039\/C9NR03060C"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.3c11496"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.6b11013"},{"key":"e_1_2_8_47_1","volume":"29","author":"Sun T.","year":"2019","journal-title":"Adv. Funct. Mater."},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trsl.2024.02.002"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40659-023-00480-z"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01887-2018"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.compbiomed.2024.108218"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvx146"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2016-0374OC"}],"container-title":["Advanced Healthcare Materials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adhm.202401909","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T11:55:45Z","timestamp":1759751745000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/adhm.202401909"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,18]]},"references-count":53,"journal-issue":{"issue":"30","published-print":{"date-parts":[[2024,12]]}},"alternative-id":["10.1002\/adhm.202401909"],"URL":"https:\/\/doi.org\/10.1002\/adhm.202401909","archive":["Portico"],"relation":{},"ISSN":["2192-2640","2192-2659"],"issn-type":[{"value":"2192-2640","type":"print"},{"value":"2192-2659","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,18]]},"assertion":[{"value":"2024-05-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-08-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2401909"}}