SiRNA-Targeting TGF-β1 Based on Nanoparticle-Coated Ureteral Stents to Inhibit Ureteral Stricture

Ureteral stricture is a difficult urological problem with no optimal solution and is the result of scar hyperplasia and fibrosis caused by ureteral injury. Preventing the formation of ureteral strictures around drug-loaded ureteral stents is at the heart of the current research. TGF-β1 is a key factor affecting collagen deposition and fiber formation. Therefore, in this study, we established a rabbit ureteral stricture model, implanted a ureteral stent loaded with TGF-β1-siRNA for treatment, and compared the histopathology of ureteral stricture and the protein expression of genes related to the formation of stricture between different groups to test their therapeutic effects. We used sustained- and slow-release properties of the nanoparticles that were confirmed through in vitro experiments. The results of the fluorescence immunoassay showed that siRNA loaded by ureteral stents had high transfection efficiency on human ureter epithelial cells in vivo. In addition, the rabbit ureteral stricture model experiment verified that TGF-β1-siRNA could effectively transfect into ureteral tissues and inhibit the expression of TGF-β1, thereby inhibiting ureteral stricture. At the same time, the images of rabbit gross anatomy specimens showed that the hydronephrosis could also be effectively relieved. In summary, all the results mentioned above suggest that ureteral stents combined with RNA interference technology and a nanoparticle delivery system have broad prospects for clinical application in the suppression of ureteral stricture.