{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T20:05:50Z","timestamp":1790712350116,"version":"4.1.0"},"reference-count":41,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2019,4,24]],"date-time":"2019-04-24T00:00:00Z","timestamp":1556064000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007479","name":"Fondazione Cassa di Risparmio di Padova e Rovigo","doi-asserted-by":"publisher","award":["13\/09"],"award-info":[{"award-number":["13\/09"]}],"id":[{"id":"10.13039\/100007479","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007479","name":"Fondazione Cassa di Risparmio di Padova e Rovigo","doi-asserted-by":"publisher","award":["17\/06_1FCR"],"award-info":[{"award-number":["17\/06_1FCR"]}],"id":[{"id":"10.13039\/100007479","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009104","name":"Universit\u00e0 Degli Studi di Modena e Reggio Emila","doi-asserted-by":"publisher","award":["FAR Unimore (PI Prof. Giovanni Tosi)"],"award-info":[{"award-number":["FAR Unimore (PI Prof. Giovanni Tosi)"]}],"id":[{"id":"10.13039\/100009104","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009104","name":"Universit\u00e0 Degli Studi di Modena e Reggio Emila","doi-asserted-by":"publisher","award":["FAR Unimore (PI Prof. Michele Zoli)"],"award-info":[{"award-number":["FAR Unimore (PI Prof. Michele Zoli)"]}],"id":[{"id":"10.13039\/100009104","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Mucopolysaccharidosis type II (MPSII) is a lysosomal storage disorder due to the deficit of the enzyme iduronate 2-sulfatase (IDS), which leads to the accumulation of glycosaminoglycans in most organ-systems, including the brain, and resulting in neurological involvement in about two-thirds of the patients. The main treatment is represented by a weekly infusion of the functional enzyme, which cannot cross the blood-brain barrier and reach the central nervous system. In this study, a tailored nanomedicine approach based on brain-targeted polymeric nanoparticles (g7-NPs), loaded with the therapeutic enzyme, was exploited. Fibroblasts from MPSII patients were treated for 7 days with NPs loaded with the IDS enzyme; an induced IDS activity like the one detected in healthy cells was measured, together with a reduction of GAG content to non-pathological levels. An in vivo short-term study in MPSII mice was performed by weekly administration of g7-NPs-IDS. Biochemical, histological, and immunohistochemical evaluations of liver and brain were performed. The 6-weeks treatment produced a significant reduction of GAG deposits in liver and brain tissues, as well as a reduction of some neurological and inflammatory markers (i.e., LAMP2, CD68, GFAP), highlighting a general improvement of the brain pathology. The g7-NPs-IDS approach allowed a brain-targeted enzyme replacement therapy. Based on these positive results, the future aim will be to optimize NP formulation further to gain a higher efficacy of the proposed approach.<\/jats:p>","DOI":"10.3390\/ijms20082014","type":"journal-article","created":{"date-parts":[[2019,4,25]],"date-time":"2019-04-25T03:02:59Z","timestamp":1556161379000},"page":"2014","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":60,"title":["Targeting Brain Disease in MPSII: Preclinical Evaluation of IDS-Loaded PLGA Nanoparticles"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0233-1677","authenticated-orcid":false,"given":"Laura","family":"Rigon","sequence":"first","affiliation":[{"name":"Department of Women\u2019s and Children\u2019s Health, University of Padova, 35128 Padova, Italy"},{"name":"Fondazione Istituto di Ricerca Pediatrica \u201cCitt\u00e0 della Speranza\u201d, 35127 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marika","family":"Salvalaio","sequence":"additional","affiliation":[{"name":"Fondazione Istituto di Ricerca Pediatrica \u201cCitt\u00e0 della Speranza\u201d, 35127 Padova, Italy"},{"name":"Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35131 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Pederzoli","sequence":"additional","affiliation":[{"name":"Fondazione Istituto di Ricerca Pediatrica \u201cCitt\u00e0 della Speranza\u201d, 35127 Padova, Italy"},{"name":"Department of Life Sciences, University of Modena and Reggio Emilia, 41124 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Legnini","sequence":"additional","affiliation":[{"name":"Department of Women\u2019s and Children\u2019s Health, University of Padova, 35128 Padova, Italy"},{"name":"Fondazione Istituto di Ricerca Pediatrica \u201cCitt\u00e0 della Speranza\u201d, 35127 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2204-1981","authenticated-orcid":false,"given":"Jason Thomas","family":"Duskey","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, University of Modena and Reggio Emilia, 41124 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2790-6481","authenticated-orcid":false,"given":"Francesca","family":"D\u2019Avanzo","sequence":"additional","affiliation":[{"name":"Department of Women\u2019s and Children\u2019s Health, University of Padova, 35128 Padova, Italy"},{"name":"Fondazione Istituto di Ricerca Pediatrica \u201cCitt\u00e0 della Speranza\u201d, 35127 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Concetta","family":"De Filippis","sequence":"additional","affiliation":[{"name":"Department of Women\u2019s and Children\u2019s Health, University of Padova, 35128 Padova, Italy"},{"name":"Fondazione Istituto di Ricerca Pediatrica \u201cCitt\u00e0 della Speranza\u201d, 35127 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2400-9910","authenticated-orcid":false,"given":"Barbara","family":"Ruozi","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, University of Modena and Reggio Emilia, 41124 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oriano","family":"Marin","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Padova, 35121 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Angela","family":"Vandelli","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, University of Modena and Reggio Emilia, 41124 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2135-2422","authenticated-orcid":false,"given":"Ilaria","family":"Ottonelli","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, University of Modena and Reggio Emilia, 41124 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Scarpa","sequence":"additional","affiliation":[{"name":"Department of Women\u2019s and Children\u2019s Health, University of Padova, 35128 Padova, Italy"},{"name":"Fondazione Istituto di Ricerca Pediatrica \u201cCitt\u00e0 della Speranza\u201d, 35127 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8318-667X","authenticated-orcid":false,"given":"Giovanni","family":"Tosi","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, University of Modena and Reggio Emilia, 41124 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosella","family":"Tomanin","sequence":"additional","affiliation":[{"name":"Department of Women\u2019s and Children\u2019s Health, University of Padova, 35128 Padova, Italy"},{"name":"Fondazione Istituto di Ricerca Pediatrica \u201cCitt\u00e0 della Speranza\u201d, 35127 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,4,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e377","DOI":"10.1542\/peds.2007-1350","article-title":"Recognition and diagnosis of mucopolysaccharidosis II (Hunter syndrome)","volume":"121","author":"Martin","year":"2008","journal-title":"Pediatrics"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1186\/s13023-014-0129-1","article-title":"Clinical efficacy of enzyme replacement therapy in paediatric Hunter patients, an independent study of 3.5 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