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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MDPI AG
2023-07-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/7/1936 |
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| author | Marina Beraza-Millor Julen Rodríguez-Castejón Jonatan Miranda Ana del Pozo-Rodríguez Alicia Rodríguez-Gascón María Ángeles Solinís |
| author_facet | Marina Beraza-Millor Julen Rodríguez-Castejón Jonatan Miranda Ana del Pozo-Rodríguez Alicia Rodríguez-Gascón María Ángeles Solinís |
| author_sort | Marina Beraza-Millor |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-11T00:44:17Z |
| format | Article |
| id | doaj.art-cd7f99f4f05048b184df3aae8ce1768f |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-11T00:44:17Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-cd7f99f4f05048b184df3aae8ce1768f2023-11-18T20:55:54ZengMDPI AGPharmaceutics1999-49232023-07-01157193610.3390/pharmaceutics15071936Novel Golden Lipid Nanoparticles with Small Interference Ribonucleic Acid for Substrate Reduction Therapy in Fabry DiseaseMarina Beraza-Millor0Julen Rodríguez-Castejón1Jonatan Miranda2Ana del Pozo-Rodríguez3Alicia Rodríguez-Gascón4María Ángeles Solinís5Pharmacokinetic, Nanotechnology and Gene Therapy Group (Pharma Nano Gene), Faculty of Pharmacy, Centro de Investigación Lascaray Ikergunea, University of Basque Country UPV/EHU, 01006 Vitoria-Gasteiz, SpainPharmacokinetic, Nanotechnology and Gene Therapy Group (Pharma Nano Gene), Faculty of Pharmacy, Centro de Investigación Lascaray Ikergunea, University of Basque Country UPV/EHU, 01006 Vitoria-Gasteiz, SpainGLUTEN3S Research Group, Faculty of Pharmacy, University of Basque Country UPV/EHU, 01006 Vitoria-Gasteiz, SpainPharmacokinetic, Nanotechnology and Gene Therapy Group (Pharma Nano Gene), Faculty of Pharmacy, Centro de Investigación Lascaray Ikergunea, University of Basque Country UPV/EHU, 01006 Vitoria-Gasteiz, SpainPharmacokinetic, Nanotechnology and Gene Therapy Group (Pharma Nano Gene), Faculty of Pharmacy, Centro de Investigación Lascaray Ikergunea, University of Basque Country UPV/EHU, 01006 Vitoria-Gasteiz, SpainPharmacokinetic, Nanotechnology and Gene Therapy Group (Pharma Nano Gene), Faculty of Pharmacy, Centro de Investigación Lascaray Ikergunea, University of Basque Country UPV/EHU, 01006 Vitoria-Gasteiz, SpainSubstrate 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.https://www.mdpi.com/1999-4923/15/7/1936substrate reduction therapysolid lipid nanoparticlessiRNAFabry diseaseGb3 synthasegold nanoparticles |
| spellingShingle | Marina Beraza-Millor Julen Rodríguez-Castejón Jonatan Miranda Ana del Pozo-Rodríguez Alicia Rodríguez-Gascón María Ángeles Solinís Novel Golden Lipid Nanoparticles with Small Interference Ribonucleic Acid for Substrate Reduction Therapy in Fabry Disease Pharmaceutics substrate reduction therapy solid lipid nanoparticles siRNA Fabry disease Gb3 synthase gold nanoparticles |
| 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 | substrate reduction therapy solid lipid nanoparticles siRNA Fabry disease Gb3 synthase gold nanoparticles |
| url | https://www.mdpi.com/1999-4923/15/7/1936 |
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