Receptor-targeted liposome-peptide-siRNA nanoparticles represent a novel and efficient therapeutic approach to prevent conjunctival fibrosis.

Yu-Wai-Man, Cynthia, Tagalakis, Aristides, Manunta, Maria D., Bailly, M, Hart, Stephen L. and Khaw, Peng T. (2016) Receptor-targeted liposome-peptide-siRNA nanoparticles represent a novel and efficient therapeutic approach to prevent conjunctival fibrosis. Scientific Reports, 6. p. 21881. ISSN 2045-2322 DOI https://doi.org/10.1038/srep21881

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Abstract

There is increasing evidence that the Myocardin-related transcription factor/Serum response factor (MRTF/SRF) pathway plays a key role in fibroblast activation and that knocking down MRTF can lead to reduced scarring and fibrosis. Here, we have developed a receptor-targeted liposome-peptide-siRNA nanoparticle as a non-viral delivery system for MRTF-B siRNA in conjunctival fibrosis. Using 50 nM siRNA, the MRTF-B gene was efficiently silenced by 76% and 72% with LYR and LER nanoparticles, respectively. The silencing efficiency was low when non-targeting peptides or siRNA alone or liposome-siRNA alone were used. LYR and LER nanoparticles also showed higher silencing efficiency than PEGylated LYR-P and LER-P nanoparticles. The nanoparticles were not cytotoxic using different liposomes, targeting peptides, and 50 nM siRNA. Three-dimensional fibroblast-populated collagen matrices were also used as a functional assay to measure contraction in vitro, and showed that MRTF-B LYR nanoparticles completely blocked matrix contraction after a single transfection treatment. In conclusion, this is the first study to develop and show that receptor-targeted liposome-peptide-siRNA nanoparticles represent an efficient and safe non-viral siRNA delivery system that could be used to prevent fibrosis after glaucoma filtration surgery and other contractile scarring conditions in the eye.

Item Type: Article
Additional Information: CY is funded by an NIHR BRC Francis Crick Institute Clinical Research Training Fellowship. Our research is supported by the National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology (NIHR BRC), the Medical Research Council, Moorfields Trustees and Moorfields Eye Charity, the Freemasons Grand Charity, the Michael and Ilse Katz Foundation, the Helen Hamlyn Trust, and Fight for Sight.
Subjects: R Medicine > RE Ophthalmology
Divisions: Biology
Date Deposited: 19 Apr 2018 13:42
URI: http://repository.edgehill.ac.uk/id/eprint/10253

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