title: α-Galactosidase-A Loaded-Nanoliposomes with Enhanced Enzymatic Activity and Intracellular Penetration.
abstract: 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.
authors.affiliation: Institut de Ciència de Materials de Barcelona (ICMAB-CSIC), Campus Universitari de Bellaterra, 08193, Cerdanyola del Vallès, Spain.|Centro de Investigación Biomédica en Red-Bioingeniería Biomateriales y Nanomedicina (CIBER-BBN), Spain.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Cabrera
authors.affiliation: Centro de Investigación Biomédica en Red-Bioingeniería Biomateriales y Nanomedicina (CIBER-BBN), Spain.|CIBBIM-Nanomedicine, Vall d'Hebron Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, 08035, Barcelona, Spain.
authors.forename: Ibane
authors.initials: I
authors.lastname: Abasolo
authors.affiliation: Centro de Investigación Biomédica en Red-Bioingeniería Biomateriales y Nanomedicina (CIBER-BBN), Spain.|Departament de Genètica i de Microbiologia, Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, 08193, Bellaterra, Spain.
authors.forename: José L
authors.initials: JL
authors.lastname: Corchero
authors.affiliation: Institut de Ciència de Materials de Barcelona (ICMAB-CSIC), Campus Universitari de Bellaterra, 08193, Cerdanyola del Vallès, Spain.|Centro de Investigación Biomédica en Red-Bioingeniería Biomateriales y Nanomedicina (CIBER-BBN), Spain.
authors.forename: Elisa
authors.initials: E
authors.lastname: Elizondo
authors.affiliation: Institut de Ciència de Materials de Barcelona (ICMAB-CSIC), Campus Universitari de Bellaterra, 08193, Cerdanyola del Vallès, Spain.|Centro de Investigación Biomédica en Red-Bioingeniería Biomateriales y Nanomedicina (CIBER-BBN), Spain.
authors.forename: Pilar Rivera
authors.initials: PR
authors.lastname: Gil
authors.affiliation: Institut de Ciència de Materials de Barcelona (ICMAB-CSIC), Campus Universitari de Bellaterra, 08193, Cerdanyola del Vallès, Spain.|Centro de Investigación Biomédica en Red-Bioingeniería Biomateriales y Nanomedicina (CIBER-BBN), Spain.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Moreno
authors.affiliation: Institut de Ciència de Materials de Barcelona (ICMAB-CSIC), Campus Universitari de Bellaterra, 08193, Cerdanyola del Vallès, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Faraudo
authors.affiliation: Institut de Ciència de Materials de Barcelona (ICMAB-CSIC), Campus Universitari de Bellaterra, 08193, Cerdanyola del Vallès, Spain.|Centro de Investigación Biomédica en Red-Bioingeniería Biomateriales y Nanomedicina (CIBER-BBN), Spain.
authors.forename: Santi
authors.initials: S
authors.lastname: Sala
authors.affiliation: Institut de Ciència de Materials de Barcelona (ICMAB-CSIC), Campus Universitari de Bellaterra, 08193, Cerdanyola del Vallès, Spain.|Centro de Investigación Biomédica en Red-Bioingeniería Biomateriales y Nanomedicina (CIBER-BBN), Spain.
authors.forename: Dolores
authors.initials: D
authors.lastname: Bueno
authors.affiliation: Institut de Ciència de Materials de Barcelona (ICMAB-CSIC), Campus Universitari de Bellaterra, 08193, Cerdanyola del Vallès, Spain.|Centro de Investigación Biomédica en Red-Bioingeniería Biomateriales y Nanomedicina (CIBER-BBN), Spain.
authors.forename: Elisabet
authors.initials: E
authors.lastname: González-Mira
authors.affiliation: ICFO-Institut de Ciencies Fotoniques, Mediterranean Technology Park, 08860, Castelldefels, Barcelona, Spain.
authors.forename: Merche
authors.initials: M
authors.lastname: Rivas
authors.affiliation: Centro de Investigación Biomédica en Red-Bioingeniería Biomateriales y Nanomedicina (CIBER-BBN), Spain.|Combinatorial Chemistry Unit, Barcelona Science Park, Baldiri Reixac 10, 08028, Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Melgarejo
authors.affiliation: Centro de Investigación Biomédica en Red-Bioingeniería Biomateriales y Nanomedicina (CIBER-BBN), Spain.|Combinatorial Chemistry Unit, Barcelona Science Park, Baldiri Reixac 10, 08028, Barcelona, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Pulido
authors.affiliation: Centro de Investigación Biomédica en Red-Bioingeniería Biomateriales y Nanomedicina (CIBER-BBN), Spain.|Institute for Research in Biomedicine, Barcelona Science Park, 08028, Barcelona, Spain.|Department of Organic Chemistry, University of Barcelona, 08028, Barcelona, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Albericio
authors.affiliation: Centro de Investigación Biomédica en Red-Bioingeniería Biomateriales y Nanomedicina (CIBER-BBN), Spain.|Combinatorial Chemistry Unit, Barcelona Science Park, Baldiri Reixac 10, 08028, Barcelona, Spain.
authors.forename: Miriam
authors.initials: M
authors.lastname: Royo
authors.affiliation: Centro de Investigación Biomédica en Red-Bioingeniería Biomateriales y Nanomedicina (CIBER-BBN), Spain.|Departament de Genètica i de Microbiologia, Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, 08193, Bellaterra, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Villaverde
authors.affiliation: ICFO-Institut de Ciencies Fotoniques, Mediterranean Technology Park, 08860, Castelldefels, Barcelona, Spain.|ICREA-Institució Catalana de Recerca i Estudis Avançats, 08010, Barcelona, Spain.
authors.forename: Maria F
authors.initials: MF
authors.lastname: García-Parajo
authors.affiliation: Centro de Investigación Biomédica en Red-Bioingeniería Biomateriales y Nanomedicina (CIBER-BBN), Spain.|CIBBIM-Nanomedicine, Vall d'Hebron Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, 08035, Barcelona, Spain.
authors.forename: Simó
authors.initials: S
authors.lastname: Schwartz
authors.affiliation: Institut de Ciència de Materials de Barcelona (ICMAB-CSIC), Campus Universitari de Bellaterra, 08193, Cerdanyola del Vallès, Spain.|Centro de Investigación Biomédica en Red-Bioingeniería Biomateriales y Nanomedicina (CIBER-BBN), Spain.
authors.forename: Nora
authors.initials: N
authors.lastname: Ventosa
authors.affiliation: Institut de Ciència de Materials de Barcelona (ICMAB-CSIC), Campus Universitari de Bellaterra, 08193, Cerdanyola del Vallès, Spain.|Centro de Investigación Biomédica en Red-Bioingeniería Biomateriales y Nanomedicina (CIBER-BBN), Spain.
authors.forename: Jaume
authors.initials: J
authors.lastname: Veciana
mesh_terms: D000818:Animals; D001011:Aorta / Q000473:pathology; D004705:Endocytosis; D042783:Endothelial Cells / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism*; D008081:Liposomes / Q000737:chemistry*; D018345:Mice, Knockout; D008958:Models, Molecular; D058726:Nanoconjugates / Q000737:chemistry / Q000648:ultrastructure; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D000519:alpha-Galactosidase / Q000378:metabolism*
chemical_list: D008081:Liposomes; D058726:Nanoconjugates; D000519:alpha-Galactosidase
keywords: Fabry disease; RGD targeting; compressed CO2; nanoliposomes; α-galactosidase A