Receptor-targeted liposome-peptide-siRNA nanoparticles represent an efficient delivery system for MRTF silencing in conjunctival fibrosis

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.

Peptide and nucleic acid-directed self-assembly of cationic nanovehicles through giant unilamellar vesicle modification: Targetable nanocomplexes for in vivo nucleic acid delivery

“…Previously, we described the use of liposome-peptide receptor-targeted nanoparticles (RTNs) for both in vitro [7][8][9][10][11] and in vivo [12][13][14][15][16][17][18] nucleic acid delivery to various sites and targets in the body. These lipopolyplexes are capable of inducing nucleic acid compaction and their protection against premature degradation in biological fluids.…”

Silencing E3 Ubiqutin ligase ITCH as a potential therapy to enhance chemotherapy efficacy in p53 mutant neuroblastoma cells

“…In our experiments, we used nanoparticles as a carrier system to deliver the ITCH siRNA in vivo. This was based on our previous findings that the receptor-targeted liposome-peptide-siRNA nanoparticle is an efficient delivery system for ex vivo and in vivo applications [49][50][51][52][53] . The formulation of the nanoparticles contains peptide ME27 which can mediate receptor-specific targeting via its interaction with integrin αvβ3 and αvβ5 on cells.…”

Nanomaterials as Protein, Peptide and Gene Delivery Agents

“…Two different liposomes LYR (non-PEGylated liposome-peptide Y-siRNA) and LER (non-PEGylated liposome-peptide ME27-siRNA) were found to be effective in causing approximately 76% silencing of the MRTF-B. This effect was found to be increased when compared with siRNA alone or the non-targeting peptides [67]. The liposomes loaded with VEGF siRNA and doclitaxel were surface modified with Angiopep-2 and neuropilin-1 receptor (tLyP-1) peptides.…”