High-Capacity Mesoporous Silica Nanocarriers of siRNA for Applications in Retinal Delivery

Author:

Ultimo Amelia1ORCID,Orzaez Mar23,Santos-Martinez Maria J.145ORCID,Martínez-Máñez Ramón3678ORCID,Marcos María D.3678ORCID,Sancenón Félix3678,Ruiz-Hernández Eduardo15

Affiliation:

1. School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin (TCD), D02 W272 Dublin, Ireland

2. Centro de Investigación Príncipe Felipe, Eduardo Primo Yúfera 3, 46012 Valencia, Spain

3. Unidad Mixta UPV-CIPF de Investigación en Mecanismos de Enfermedades y Nanomedicina, Universitat Politècnica de València, Centro de Investigación Príncipe Felipe, 46012 Valencia, Spain

4. School of Medicine, Trinity College Dublin (TCD), D02 R590 Dublin, Ireland

5. Trinity Biomedical Sciences Institute, Trinity College Dublin (TCD), D02 R590 Dublin, Ireland

6. Instituto Interuniversitario de Reconocimiento Molecular y Desarrollo Tecnológico (IDM), Universitat Politècnica de València, Universitat de València, 46022 Valencia, Spain

7. Unidad Mixta de Investigación en Nanomedicina y Sensores, Universitat Politècnica de València, Instituto de Investigación Sanitaria La Fe, 46026 Valencia, Spain

8. CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), 28029 Madrid, Spain

Abstract

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.

Funder

Wellcome Trust Institutional Strategic Support Fund

European Research Council

European Union’s Horizon 2020 research and Innovation programme

Spanish Government

Generalitat Valenciana

European Union’s Horizon 2020 research and innovation programme

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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