{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T09:01:41Z","timestamp":1790067701417,"version":"4.0.1"},"reference-count":27,"publisher":"American Association for the Advancement of Science (AAAS)","funder":[{"DOI":"10.13039\/100007363","name":"Fondazione Citt\u00e0 della Speranza","doi-asserted-by":"publisher","award":["21\/09 IRP"],"award-info":[{"award-number":["21\/09 IRP"]}],"id":[{"id":"10.13039\/100007363","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003500","name":"Universit\u00e0 degli Studi di Padova","doi-asserted-by":"publisher","award":["BIRD-2024"],"award-info":[{"award-number":["BIRD-2024"]}],"id":[{"id":"10.13039\/501100003500","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["spj.science.org"],"crossmark-restriction":true},"short-container-title":["Biomater Res"],"published-print":{"date-parts":[[2026,1,1]]},"abstract":"<jats:p>Anti-angiogenic therapies targeting the vascular endothelial growth factor (VEGF) axis have achieved transient benefits, as tumors rapidly activate compensatory vascular programs. Here, we present a bioinspired nanoplatform that reproduces the anti-angiogenic signaling of mesenchymal-stromal-cell-derived extracellular vesicles (EVs) by delivering the endogenous metalloproteinase inhibitor tissue inhibitor of metalloproteinases-1 (TIMP-1). Poly(methyl methacrylate) nanoparticles (NP_TIMP1) were engineered to retain TIMP-1 bioactivity, inhibit matrix metalloproteinase activity, and efficiently interact with endothelial cells. In\u00a0vitro, NP_TIMP1 suppressed endothelial sprouting and tip-cell formation in 2-dimensional and 3-dimensional microfluidic systems. In zebrafish patient-derived xenografts of Ewing sarcoma, NP_TIMP1 localized to tumor-associated vessels and substantially reduced vascular infiltration, reproducing the efficacy of TIMP-1-enriched EVs. In contrast, soluble TIMP-1 failed to elicit these effects, indicating that nanoparticle-mediated delivery enhances protein stability and spatial engagement with the endothelium. This study establishes TIMP-1 as a key stromal regulator of angiogenesis and demonstrates that EV-mimetic nanoparticles can recapitulate its therapeutic potential, providing a scalable bioengineering approach to overcome the limitations of natural vesicles and develop next-generation anti-angiogenic nanotherapeutics.<\/jats:p>","DOI":"10.34133\/bmr.0408","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T20:24:16Z","timestamp":1787862256000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark_01","source":"Crossref","is-referenced-by-count":0,"title":["Bioinspired TIMP-1 Nanoparticles Mimic Extracellular Vesicle Anti-angiogenic Activity in Ewing Sarcoma"],"prefix":"10.34133","volume":"30","author":[{"given":"Cristina","family":"Liboni","sequence":"first","affiliation":[{"name":"Laboratory of Immunity and Inflammation, Department of Biomedical Sciences, \rUniversity of Padova, Padua, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Boaron","sequence":"additional","affiliation":[{"name":"Laboratory of Immunity and Inflammation, Department of Biomedical Sciences, \rUniversity of Padova, Padua, Italy."},{"name":"Pediatric Research Institute Citt\u00e0 della Speranza Foundation","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Corallo","sequence":"additional","affiliation":[{"name":"Pediatric Research Institute Citt\u00e0 della Speranza Foundation","place":["Italy"]},{"name":"Laboratory of Target Discovery and Biology of Neuroblastoma, \rPediatric Research Institute Citt\u00e0 della Speranza Foundation, Padua, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3886-4360","authenticated-orcid":false,"given":"Sanja","family":"Aveic","sequence":"additional","affiliation":[{"name":"Pediatric Research Institute Citt\u00e0 della Speranza Foundation","place":["Italy"]},{"name":"Laboratory of Target Discovery and Biology of Neuroblastoma, \rPediatric Research Institute Citt\u00e0 della Speranza Foundation, Padua, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Ballestri","sequence":"additional","affiliation":[{"name":"Institute for Organic Synthesis and Photoreactivity (ISOF), National Research Council of Italy (CNR), Bologna, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"S\u00e1nchez-Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Laboratory of Immunity and Inflammation, Department of Biomedical Sciences, \rUniversity of Padova, Padua, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra Maria","family":"Testa","sequence":"additional","affiliation":[{"name":"Laboratory of Immunity and Inflammation, Department of Biomedical Sciences, \rUniversity of Padova, Padua, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Ferroni","sequence":"additional","affiliation":[{"name":"Institute for Organic Synthesis and Photoreactivity (ISOF), National Research Council of Italy (CNR), Bologna, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8358-3437","authenticated-orcid":false,"given":"Greta","family":"Varchi","sequence":"additional","affiliation":[{"name":"Institute for Organic Synthesis and Photoreactivity (ISOF), National Research Council of Italy (CNR), Bologna, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Viola","sequence":"additional","affiliation":[{"name":"Laboratory of Immunity and Inflammation, Department of Biomedical Sciences, \rUniversity of Padova, Padua, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5734-5913","authenticated-orcid":true,"given":"Roberta","family":"Angioni","sequence":"additional","affiliation":[{"name":"Laboratory of Immunity and Inflammation, Department of Biomedical Sciences, \rUniversity of Padova, Padua, Italy."},{"name":"Pediatric Research Institute Citt\u00e0 della Speranza Foundation","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","published-online":{"date-parts":[[2026,9,22]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s43018-024-00780-7"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1359-6446(03)02686-2"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.00221"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1097\/CCO.0000000000001048"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.12566"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.24844"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.3390\/medsci12010004"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.611039"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-019-0223-5"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1080\/20013078.2020.1757900"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/jev2.12404"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm.2017.125"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2012.202"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2014.09.028"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/stcltm\/szad070"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15010092"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-67289-8"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0703446104"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2007.412"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature23647"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2016.33"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/s44222-024-00255-5"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-020-0090-8"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-026-15656-5"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.00454"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2019.00021"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2024.12412"}],"container-title":["Biomaterials Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/spj.science.org\/doi\/pdf\/10.34133\/bmr.0408","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T08:17:34Z","timestamp":1790065054000},"score":1,"resource":{"primary":{"URL":"https:\/\/spj.science.org\/doi\/10.34133\/bmr.0408"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,1]]},"references-count":27,"alternative-id":["10.34133\/bmr.0408"],"URL":"https:\/\/doi.org\/10.34133\/bmr.0408","relation":{},"ISSN":["2055-7124"],"issn-type":[{"value":"2055-7124","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,1]]},"assertion":[{"value":"2026-01-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-06","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-01","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"0408"}}