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.
Targeting Brain Disease in MPSII: Preclinical Evaluation of IDS-Loaded PLGA Nanoparticles / Rigon, Laura; Salvalaio, Marika; Pederzoli, Francesca; Legnini, Elisa; Duskey, Jason Thomas; D'Avanzo, Francesca; De Filippis, Concetta; Ruozi, Barbara; Marin, Oriano; Vandelli, Maria Angela; Ottonelli, Ilaria; Scarpa, Maurizio; Tosi, Giovanni; Tomanin, Rosella. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1422-0067. - 20:8(2019), pp. 1-15.
Data di pubblicazione: | 2019 |
Titolo: | Targeting Brain Disease in MPSII: Preclinical Evaluation of IDS-Loaded PLGA Nanoparticles |
Autore/i: | Rigon, Laura; Salvalaio, Marika; Pederzoli, Francesca; Legnini, Elisa; Duskey, Jason Thomas; D'Avanzo, Francesca; De Filippis, Concetta; Ruozi, Barbara; Marin, Oriano; Vandelli, Maria Angela; Ottonelli, Ilaria; Scarpa, Maurizio; Tosi, Giovanni; Tomanin, Rosella |
Autore/i UNIMORE: | |
Digital Object Identifier (DOI): | http://dx.doi.org/10.3390/ijms20082014 |
Rivista: | |
Volume: | 20 |
Fascicolo: | 8 |
Pagina iniziale: | 1 |
Pagina finale: | 15 |
Codice identificativo ISI: | WOS:000467648700212 |
Codice identificativo Scopus: | 2-s2.0-85065389215 |
Codice identificativo Pubmed: | 31022913 |
Citazione: | Targeting Brain Disease in MPSII: Preclinical Evaluation of IDS-Loaded PLGA Nanoparticles / Rigon, Laura; Salvalaio, Marika; Pederzoli, Francesca; Legnini, Elisa; Duskey, Jason Thomas; D'Avanzo, Francesca; De Filippis, Concetta; Ruozi, Barbara; Marin, Oriano; Vandelli, Maria Angela; Ottonelli, Ilaria; Scarpa, Maurizio; Tosi, Giovanni; Tomanin, Rosella. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1422-0067. - 20:8(2019), pp. 1-15. |
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