| Autor: |
Rigon L; Department of Women's and Children's Health, University of Padova, 35128 Padova, Italy. laura.rigon@unipd.it.; Fondazione Istituto di Ricerca Pediatrica 'Città della Speranza', 35127 Padova, Italy. laura.rigon@unipd.it., Salvalaio M; Fondazione Istituto di Ricerca Pediatrica 'Città della Speranza', 35127 Padova, Italy. marika.salvalaio@unipd.it.; Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35131 Padova, Italy. marika.salvalaio@unipd.it., Pederzoli F; Fondazione Istituto di Ricerca Pediatrica 'Città della Speranza', 35127 Padova, Italy. francesca.pederzoli@unimore.it.; Department of Life Sciences, University of Modena and Reggio Emilia, 41124 Modena, Italy. francesca.pederzoli@unimore.it., Legnini E; Department of Women's and Children's Health, University of Padova, 35128 Padova, Italy. elisalg@yahoo.it.; Fondazione Istituto di Ricerca Pediatrica 'Città della Speranza', 35127 Padova, Italy. elisalg@yahoo.it., Duskey JT; Department of Life Sciences, University of Modena and Reggio Emilia, 41124 Modena, Italy. jasonthomas.duskey@unimore.it., D'Avanzo F; Department of Women's and Children's Health, University of Padova, 35128 Padova, Italy. frale100@gmail.com.; Fondazione Istituto di Ricerca Pediatrica 'Città della Speranza', 35127 Padova, Italy. frale100@gmail.com., De Filippis C; Department of Women's and Children's Health, University of Padova, 35128 Padova, Italy. concetta.defilippis93@gmail.com.; Fondazione Istituto di Ricerca Pediatrica 'Città della Speranza', 35127 Padova, Italy. concetta.defilippis93@gmail.com., Ruozi B; Department of Life Sciences, University of Modena and Reggio Emilia, 41124 Modena, Italy. barbara.ruozi@unimore.it., Marin O; Department of Biomedical Sciences, University of Padova, 35121 Padova, Italy. oriano.marin@unipd.it., Vandelli MA; Department of Life Sciences, University of Modena and Reggio Emilia, 41124 Modena, Italy. mariaangela.vandelli@unimore.it., Ottonelli I; Department of Life Sciences, University of Modena and Reggio Emilia, 41124 Modena, Italy. ilaria.ottonelli@unimore.it., Scarpa M; Department of Women's and Children's Health, University of Padova, 35128 Padova, Italy. maurizio.scarpa@unipd.it.; Fondazione Istituto di Ricerca Pediatrica 'Città della Speranza', 35127 Padova, Italy. maurizio.scarpa@unipd.it., Tosi G; Department of Life Sciences, University of Modena and Reggio Emilia, 41124 Modena, Italy. gtosi@unimore.it., Tomanin R; Department of Women's and Children's Health, University of Padova, 35128 Padova, Italy. rosella.tomanin@unipd.it.; Fondazione Istituto di Ricerca Pediatrica 'Città della Speranza', 35127 Padova, Italy. rosella.tomanin@unipd.it. |
| Abstrakt: |
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. |
