High-Capacity Mesoporous Silica Nanocarriers of siRNA for Applications in Retinal Delivery
The main cause of subretinal neovascularisation in wet age-related macular degeneration (AMD) is an abnormal expression in the retinal pigment epithelium (RPE) of the vascular endothelial growth factor (VEGF). Current approaches for the treatment of AMD present considerable issues that could be over...
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| Format: | Article |
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MDPI AG
2023-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/3/2753 |
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| author | Amelia Ultimo Mar Orzaez Maria J. Santos-Martinez Ramón Martínez-Máñez María D. Marcos Félix Sancenón Eduardo Ruiz-Hernández |
| author_facet | Amelia Ultimo Mar Orzaez Maria J. Santos-Martinez Ramón Martínez-Máñez María D. Marcos Félix Sancenón Eduardo Ruiz-Hernández |
| author_sort | Amelia Ultimo |
| collection | DOAJ |
| description | The main cause of subretinal neovascularisation in wet age-related macular degeneration (AMD) is an abnormal expression in the retinal pigment epithelium (RPE) of the vascular endothelial growth factor (VEGF). Current approaches for the treatment of AMD present considerable issues that could be overcome by encapsulating anti-VEGF drugs in suitable nanocarriers, thus providing better penetration, higher retention times, and sustained release. In this work, the ability of large pore mesoporous silica nanoparticles (LP-MSNs) to transport and protect nucleic acid molecules is exploited to develop an innovative LP-MSN-based nanosystem for the topical administration of anti-VEGF siRNA molecules to RPE cells. siRNA is loaded into LP-MSN mesopores, while the external surface of the nanodevices is functionalised with polyethylenimine (PEI) chains that allow the controlled release of siRNA and promote endosomal escape to facilitate cytosolic delivery of the cargo. The successful results obtained for VEGF silencing in ARPE-19 RPE cells demonstrate that the designed nanodevice is suitable as an siRNA transporter. |
| first_indexed | 2024-03-11T09:40:08Z |
| format | Article |
| id | doaj.art-a696d8bad79142379be54cbe40123b6b |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T09:40:08Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-a696d8bad79142379be54cbe40123b6b2023-11-16T17:01:52ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-02-01243275310.3390/ijms24032753High-Capacity Mesoporous Silica Nanocarriers of siRNA for Applications in Retinal DeliveryAmelia Ultimo0Mar Orzaez1Maria J. Santos-Martinez2Ramón Martínez-Máñez3María D. Marcos4Félix Sancenón5Eduardo Ruiz-Hernández6School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin (TCD), D02 W272 Dublin, IrelandCentro de Investigación Príncipe Felipe, Eduardo Primo Yúfera 3, 46012 Valencia, SpainSchool of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin (TCD), D02 W272 Dublin, IrelandUnidad Mixta UPV-CIPF de Investigación en Mecanismos de Enfermedades y Nanomedicina, Universitat Politècnica de València, Centro de Investigación Príncipe Felipe, 46012 Valencia, SpainUnidad Mixta UPV-CIPF de Investigación en Mecanismos de Enfermedades y Nanomedicina, Universitat Politècnica de València, Centro de Investigación Príncipe Felipe, 46012 Valencia, SpainUnidad Mixta UPV-CIPF de Investigación en Mecanismos de Enfermedades y Nanomedicina, Universitat Politècnica de València, Centro de Investigación Príncipe Felipe, 46012 Valencia, SpainSchool of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin (TCD), D02 W272 Dublin, IrelandThe main cause of subretinal neovascularisation in wet age-related macular degeneration (AMD) is an abnormal expression in the retinal pigment epithelium (RPE) of the vascular endothelial growth factor (VEGF). Current approaches for the treatment of AMD present considerable issues that could be overcome by encapsulating anti-VEGF drugs in suitable nanocarriers, thus providing better penetration, higher retention times, and sustained release. In this work, the ability of large pore mesoporous silica nanoparticles (LP-MSNs) to transport and protect nucleic acid molecules is exploited to develop an innovative LP-MSN-based nanosystem for the topical administration of anti-VEGF siRNA molecules to RPE cells. siRNA is loaded into LP-MSN mesopores, while the external surface of the nanodevices is functionalised with polyethylenimine (PEI) chains that allow the controlled release of siRNA and promote endosomal escape to facilitate cytosolic delivery of the cargo. The successful results obtained for VEGF silencing in ARPE-19 RPE cells demonstrate that the designed nanodevice is suitable as an siRNA transporter.https://www.mdpi.com/1422-0067/24/3/2753age-related macular degenerationlarge pore mesoporous silica nanoparticlessiRNA deliveryVEGF silencing |
| spellingShingle | Amelia Ultimo Mar Orzaez Maria J. Santos-Martinez Ramón Martínez-Máñez María D. Marcos Félix Sancenón Eduardo Ruiz-Hernández High-Capacity Mesoporous Silica Nanocarriers of siRNA for Applications in Retinal Delivery International Journal of Molecular Sciences age-related macular degeneration large pore mesoporous silica nanoparticles siRNA delivery VEGF silencing |
| title | High-Capacity Mesoporous Silica Nanocarriers of siRNA for Applications in Retinal Delivery |
| title_full | High-Capacity Mesoporous Silica Nanocarriers of siRNA for Applications in Retinal Delivery |
| title_fullStr | High-Capacity Mesoporous Silica Nanocarriers of siRNA for Applications in Retinal Delivery |
| title_full_unstemmed | High-Capacity Mesoporous Silica Nanocarriers of siRNA for Applications in Retinal Delivery |
| title_short | High-Capacity Mesoporous Silica Nanocarriers of siRNA for Applications in Retinal Delivery |
| title_sort | high capacity mesoporous silica nanocarriers of sirna for applications in retinal delivery |
| topic | age-related macular degeneration large pore mesoporous silica nanoparticles siRNA delivery VEGF silencing |
| url | https://www.mdpi.com/1422-0067/24/3/2753 |
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