Published February 1, 2023 | Version v1
Journal article Open

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

  • 1. School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin (TCD)
  • 2. Centro de Investigación Príncipe Felipe
  • 3. Unidad Mixta UPV-CIPF de Investigación en Mecanismos de Enfermedades y Nanomedicina, Universitat Politècnica de València, Centro de Investigación Príncipe Felipe
  • 4. School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin
  • 5. School of Medicine, Trinity College Dublin
  • 6. Trinity Biomedical Sciences Institute, Trinity College Dublin
  • 7. Instituto Interuniversitario de Reconocimiento Molecular y Desarrollo Tecnológico (IDM), Universitat Politècnica de València, Universitat de València
  • 8. Unidad Mixta de Investigación en Nanomedicina y Sensores, Universitat Politècnica de València, Instituto de Investigación Sanitaria La Fe
  • 9. CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN)
  • 10. Trinity Biomedical Sciences Institute, Trinity College Dublin (TCD)

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.

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Additional details

Funding

NANOFACTS – Networking Activities for Nanotechnology-Facilitated Cancer Theranostics 952259
European Commission