2026-04-14T05:48:29Zhttps://recercat.cat/oai/request

oai:recercat.cat:10230/607302025-12-26T11:21:57Zcom_2072_6col_2072_452952

00925njm 22002777a 4500 dc Cabrera, Ingrid author Abasolo, Ibane author Corchero, José L. author Elizondo, Elisa author Rivera Gil, Pilar, 1976- author Moreno, Evelyn author Faraudo, Jordi author Sala, Santi author Bueno, Dolores author González Mira, Elisabet author Rivas, Merche author Melgarejo, Marta author Pulido, Daniel author Albericio, Fernando author Royo, Miriam author Villaverde, Antonio author García Parajó, María F. author Schwartz Jr, Simó author Ventosa, Nora author Veciana, Jaume author 2024-07-11T11:24:00Z 2024-07-11T11:24:00Z 2016 Lysosomal storage disorders (LSD) are caused by lysosomal dysfunction usually as a consequence of deficiency of a single enzyme required for the metabolism of macromolecules, such as lipids, glycoproteins, and mucopolysaccharides. For instance, the lack of α-galactosidase A (GLA) activity in Fabry disease patients causes the accumulation of glycosphingolipids in the vasculature leading to multiple organ pathology. Enzyme replacement therapy, which is the most common treatment of LSD, exhibits several drawbacks mainly related to the instability and low efficacy of the exogenously administered therapeutic enzyme. In this work, the unprecedented increased enzymatic activity and intracellular penetration achieved by the association of a human recombinant GLA to nanoliposomes functionalized with Arginine-Glycine-Aspartic acid (RGD) peptides is reported. Moreover, these new GLA loaded nanoliposomes lead to a higher efficacy in the reduction of the GLA substrate named globotriasylceramide in a cellular model of Fabry disease, than that achieved by the same concentration of the free enzyme. The preparation of these new liposomal formulations by DELOS-SUSP, based on the depressurization of a CO2 -expanded liquid organic solution, shows the great potential of this CO2 -based methodology for the one-step production of protein-nanoliposome conjugates as bioactive nanomaterials with therapeutic interest. Fabry disease RGD targeting Compressed CO2 Nanoliposomes α-galactosidase A α-Galactosidase-A loaded-nanoliposomes with enhanced enzymatic activity and intracellular penetration