Nanoparticle-mediated delivery of TGF-β1 miRNA plasmid for preventing flexor tendon adhesion formation.
Treatment of the disrupted digital flexor tendon is troublesome because of the lack of sufficient healing capacity and the formation of adhesions. Sustained gene delivery may be a promising approach of modulating gene expression in enhancing tendon healing and decreasing adhesions. In this study, a microRNA-based RNAi plasmid was used to specifically silence the expression of TGF-β1 gene associated with scar and adhesion formation in the flexor tendons. The miRNA plasmids were complexed with polylactic-co-glycolic acid (PLGA) nanoparticles to form nanoparticle/TGF-β1 miRNA plasmid (nanoparticle/plasmid) complexes. In vitro and in vivo transfection efficiencies experiments against tenocytes revealed that nanoparticle/plasmid complexes have significantly superior transfection efficiency over the lipofectamine/plasmid complexes. The gene and protein expression associated with adhesion of tendon treated with nanoparticle/plasmid complexes were evaluated by real-time PCR and immunoblotting. The grading of adhesions for tendons treated with nanoparticle/plasmid complexes was less severe than that treated with the nanoparticle/mock plasmid complexes. However, the ultimate strength of repaired tendons treated with nanoparticle/plasmid complexes was significantly lower than that of tendons treated with the nanoparticle/mock plasmid complexes.
Hand Surgery Research Center, Department of Hand Surgery, Affiliated Hospital of Nantong University, Nantong 226001, PR China.
Youlang
Y
Zhou
Luzhong
L
Zhang
Weixin
W
Zhao
Yafang
Y
Wu
Changlai
C
Zhu
Yumin
Y
Yang
D000818:Animals; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D002645:Chickens; D019344:Lactic Acid / Q000737:chemistry; D035683:MicroRNAs / Q000235:genetics*; D053758:Nanoparticles / Q000737:chemistry*; D010957:Plasmids / Q000235:genetics*; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D060888:Real-Time Polymerase Chain Reaction; D013710:Tendons / Q000166:cytology*; D053773:Transforming Growth Factor beta1 / Q000235:genetics*
D035683:MicroRNAs; D053773:Transforming Growth Factor beta1; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
Flexor tendon; Gene delivery; Nanoparticle; Transfection efficiency; microRNA