Journal
POLYMERS
Volume 12, Issue 7, Pages -Publisher
MDPI
DOI: 10.3390/polym12071508
Keywords
fibrosis; myofibroblasts; activated stellate cells; vimentin; NF-kappa B decoy oligonucleotides; HSP47; siRNA
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Funding
- JSPS KAKENHI [JP19K12804]
- Cooperative Research program of Network Joint Research Center for Materials and Devices - JSPS KAKENHI [JP19K12804]
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Targeting myofibroblasts and activated stellate cells in lesion sites of fibrotic tissues is an important approach to treat fibroses. Herein, we focused on targeting the cytoskeletal proteins vimentin, which are reportedly highly expressed on the surface of these cells and have N-acetylglucosamine (GlcNAc)-binding activity. A GlcNAc-bearing polymer synthesized via radical polymerization with a reversible addition-fragmentation chain transfer reagent has been previously found to interact with cell-surface vimentin-expressing cells. We designed a GlcNAc-bearing polymer-conjugated polyethyleneimine (PEI), as the gene carrier to target cell-surface vimentin-expressing cells and specifically deliver nuclear factor-kappa B decoy oligonucleotides (ODNs) and heat shock protein 47 (HSP47)-small interfering RNA (siRNA) to normal human dermal fibroblasts (NHDFs) that express cell-surface vimentin. The results showed that the expression of tumor necrosis factor-alpha in lipopolysaccharide-stimulated NHDFs and HSP47 in transforming growth factor-beta 1-stimulated NHDFs was suppressed by cellular uptake of the GlcNAc-bearing polymer-conjugated PEI/nuclear factor (NF)-kappa B decoy ODNs and HSP47-siRNA complexes through cell-surface vimentin, respectively. These findings suggest that the effective and specific delivery of ODNs and siRNA for cell-surface vimentin-expressing cells such as myofibroblasts and activated stellate cells can be achieved using GlcNAc-bearing polymer-conjugated PEI. This therapeutic approach could prove advantageous to prevent the promotion of various fibroses.
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