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Novel Golden Lipid Nanoparticles with Small Interference Ribonucleic Acid for Substrate Reduction Therapy in Fabry Disease

Substrate reduction therapy (SRT) has been proposed as a new gene therapy for Fabry disease (FD) to prevent the formation of globotriaosylceramide (Gb3). Nanomedicines containing different siRNA targeted to Gb3 synthase (Gb3S) were designed. Formulation factors, such as the composition, solid lipid...

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Autores principales: Beraza-Millor, Marina, Rodríguez-Castejón, Julen, Miranda, Jonatan, del Pozo-Rodríguez, Ana, Rodríguez-Gascón, Alicia, Solinís, María Ángeles
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10385692/
https://www.ncbi.nlm.nih.gov/pubmed/37514122
http://dx.doi.org/10.3390/pharmaceutics15071936
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author Beraza-Millor, Marina
Rodríguez-Castejón, Julen
Miranda, Jonatan
del Pozo-Rodríguez, Ana
Rodríguez-Gascón, Alicia
Solinís, María Ángeles
author_facet Beraza-Millor, Marina
Rodríguez-Castejón, Julen
Miranda, Jonatan
del Pozo-Rodríguez, Ana
Rodríguez-Gascón, Alicia
Solinís, María Ángeles
author_sort Beraza-Millor, Marina
collection PubMed
description Substrate reduction therapy (SRT) has been proposed as a new gene therapy for Fabry disease (FD) to prevent the formation of globotriaosylceramide (Gb3). Nanomedicines containing different siRNA targeted to Gb3 synthase (Gb3S) were designed. Formulation factors, such as the composition, solid lipid nanoparticles (SLNs) preparation method and the incorporation of different ligands, such as gold nanoparticles (GNs), protamine (P) and polysaccharides, were evaluated. The new siRNA–golden LNPs were efficiently internalized in an FD cell model (IMFE-1), with GNs detected in the cytoplasm and in the nucleus. Silencing efficacy (measured by RT-qPCR) depended on the final composition and method of preparation, with silencing rates up to 90% (expressed as the reduction in Gb3S-mRNA). GNs conferred a higher system efficacy and stability without compromising cell viability and hemocompatibility. Immunocytochemistry assays confirmed Gb3S silencing for at least 15 days with the most effective formulations. Overall, these results highlight the potential of the new siRNA–golden LNP system as a promising nanomedicine to address FD by specific SRT.
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spelling pubmed-103856922023-07-30 Novel Golden Lipid Nanoparticles with Small Interference Ribonucleic Acid for Substrate Reduction Therapy in Fabry Disease Beraza-Millor, Marina Rodríguez-Castejón, Julen Miranda, Jonatan del Pozo-Rodríguez, Ana Rodríguez-Gascón, Alicia Solinís, María Ángeles Pharmaceutics Article Substrate reduction therapy (SRT) has been proposed as a new gene therapy for Fabry disease (FD) to prevent the formation of globotriaosylceramide (Gb3). Nanomedicines containing different siRNA targeted to Gb3 synthase (Gb3S) were designed. Formulation factors, such as the composition, solid lipid nanoparticles (SLNs) preparation method and the incorporation of different ligands, such as gold nanoparticles (GNs), protamine (P) and polysaccharides, were evaluated. The new siRNA–golden LNPs were efficiently internalized in an FD cell model (IMFE-1), with GNs detected in the cytoplasm and in the nucleus. Silencing efficacy (measured by RT-qPCR) depended on the final composition and method of preparation, with silencing rates up to 90% (expressed as the reduction in Gb3S-mRNA). GNs conferred a higher system efficacy and stability without compromising cell viability and hemocompatibility. Immunocytochemistry assays confirmed Gb3S silencing for at least 15 days with the most effective formulations. Overall, these results highlight the potential of the new siRNA–golden LNP system as a promising nanomedicine to address FD by specific SRT. MDPI 2023-07-12 /pmc/articles/PMC10385692/ /pubmed/37514122 http://dx.doi.org/10.3390/pharmaceutics15071936 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Beraza-Millor, Marina
Rodríguez-Castejón, Julen
Miranda, Jonatan
del Pozo-Rodríguez, Ana
Rodríguez-Gascón, Alicia
Solinís, María Ángeles
Novel Golden Lipid Nanoparticles with Small Interference Ribonucleic Acid for Substrate Reduction Therapy in Fabry Disease
title Novel Golden Lipid Nanoparticles with Small Interference Ribonucleic Acid for Substrate Reduction Therapy in Fabry Disease
title_full Novel Golden Lipid Nanoparticles with Small Interference Ribonucleic Acid for Substrate Reduction Therapy in Fabry Disease
title_fullStr Novel Golden Lipid Nanoparticles with Small Interference Ribonucleic Acid for Substrate Reduction Therapy in Fabry Disease
title_full_unstemmed Novel Golden Lipid Nanoparticles with Small Interference Ribonucleic Acid for Substrate Reduction Therapy in Fabry Disease
title_short Novel Golden Lipid Nanoparticles with Small Interference Ribonucleic Acid for Substrate Reduction Therapy in Fabry Disease
title_sort novel golden lipid nanoparticles with small interference ribonucleic acid for substrate reduction therapy in fabry disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10385692/
https://www.ncbi.nlm.nih.gov/pubmed/37514122
http://dx.doi.org/10.3390/pharmaceutics15071936
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