title: Noncovalenly PEGylated CTGF siRNA/PDMAEMA complex for pulmonary treatment of bleomycin-induced lung fibrosis.
abstract: On the basis of wide biomedical applications of methacrylate polymers, we previously developed noncovalently post-PEGylated ternary complex of siRNA using poly(dimethylamino)ethylmethacrylate (PDMAEMA) and its copolymer with poly(α-methylether-ω-methacrylate-ethyleneglycol) [PMAPEG]. In this work, we investigated the antifibrotic effect of connective tissue growth factor siRNA (siCTGF)/PDMAEMA/PDMAEMA-b-PMAPEG complex for the treatment of bleomycin-induced pulmonary fibrosis. After orotracheal administration to fibrotic Sprague Dawley (SD) model rats, FAM-labeled siCTGF complex was effectively delivered to the cells in the lung. The siCTGF ternary complex resulted in a significant reduction in target gene expression, collagen deposition, inflammatory cytokines production, and drastic attenuation of pulmonary fibrosis in pathophysiological analysis. Furthermore, the survival rate was remarkably increased to the statistically significant level in comparison with the scrambled siCTGF treatment group.
authors.affiliation: Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University, School of Medicine, Seoul 135-710, Republic of Korea.
authors.forename: Dong Kyung
authors.initials: DK
authors.lastname: Sung
authors.forename: Won Ho
authors.initials: WH
authors.lastname: Kong
authors.forename: Kitae
authors.initials: K
authors.lastname: Park
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Kim
authors.forename: Mi Young
authors.initials: MY
authors.lastname: Kim
authors.forename: Hyemin
authors.initials: H
authors.lastname: Kim
authors.forename: Sei Kwang
authors.initials: SK
authors.lastname: Hahn
mesh_terms: D000818:Animals; D001761:Bleomycin; D055513:Connective Tissue Growth Factor / Q000235:genetics; D008297:Male; D008689:Methacrylates / Q000737:chemistry*; D053769:Nanocapsules / Q000008:administration & dosage* / Q000737:chemistry; D009757:Nylons / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000235:genetics* / Q000628:therapy*; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome
chemical_list: C526317:CCN2 protein, human; D008689:Methacrylates; D053769:Nanocapsules; D009757:Nylons; D034741:RNA, Small Interfering; C407037:poly(2-(dimethylamino)ethyl methacrylate); D001761:Bleomycin; D055513:Connective Tissue Growth Factor; D011092:Polyethylene Glycols