SCIENTIFIC HIGHLIGHTS

α-Galactosidase-A Loaded-Nanoliposomes with Enhanced Enzymatic Activity and Intracellular Penetration
12 July 2016

Ingrid Cabrera, Ibane Abasolo, José L. Corchero, Elisa Elizondo, Pilar Rivera Gil, Evelyn Moreno, Jordi Faraudo, Santi Sala, Dolores Bueno, Elisabet González-Mira, Merche Rivas, Marta Melgarejo, Daniel Pulido, Fernando Albericio, Miriam Royo, Antonio Villaverde, Maria F. García-Parajo, Simó Schwartz Jr., Nora Ventosa* and Jaume Veciana* Advanced Healthcare Materials.Volume 5, Issue 7, pages 829–840, April 6, 2016 DOI: 10.1002/adhm.201500746

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.

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Bioactive materials for therapy and diagnosis

α-Galactosidase-A Loaded-Nanoliposomes with Enhanced Enzymatic Activity and Intracellular Penetration



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