{"title":"SiRNA-Targeting TGF-β1 Based on Nanoparticle-Coated Ureteral Stents to Inhibit Ureteral Stricture.","authors":"Wei Meng, Ningning Li, Feng Lv, Bo Chen, Shuaijiang Lu, Jiayi Zhang, Tong Zhang, Qianyu Tao, Youlang Zhou, Limin Ma, Yangbo Guan","doi":"10.1021/acsbiomaterials.4c01925","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":""},"PeriodicalIF":5.4000,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Biomaterials Science & Engineering","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.1021/acsbiomaterials.4c01925","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MATERIALS SCIENCE, BIOMATERIALS","Score":null,"Total":0}
引用次数: 0
Abstract
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.
期刊介绍：
ACS Biomaterials Science & Engineering is the leading journal in the field of biomaterials, serving as an international forum for publishing cutting-edge research and innovative ideas on a broad range of topics:
Applications and Health – implantable tissues and devices, prosthesis, health risks, toxicology
Bio-interactions and Bio-compatibility – material-biology interactions, chemical/morphological/structural communication, mechanobiology, signaling and biological responses, immuno-engineering, calcification, coatings, corrosion and degradation of biomaterials and devices, biophysical regulation of cell functions
Characterization, Synthesis, and Modification – new biomaterials, bioinspired and biomimetic approaches to biomaterials, exploiting structural hierarchy and architectural control, combinatorial strategies for biomaterials discovery, genetic biomaterials design, synthetic biology, new composite systems, bionics, polymer synthesis
Controlled Release and Delivery Systems – biomaterial-based drug and gene delivery, bio-responsive delivery of regulatory molecules, pharmaceutical engineering
Healthcare Advances – clinical translation, regulatory issues, patient safety, emerging trends
Imaging and Diagnostics – imaging agents and probes, theranostics, biosensors, monitoring
Manufacturing and Technology – 3D printing, inks, organ-on-a-chip, bioreactor/perfusion systems, microdevices, BioMEMS, optics and electronics interfaces with biomaterials, systems integration
Modeling and Informatics Tools – scaling methods to guide biomaterial design, predictive algorithms for structure-function, biomechanics, integrating bioinformatics with biomaterials discovery, metabolomics in the context of biomaterials
Tissue Engineering and Regenerative Medicine – basic and applied studies, cell therapies, scaffolds, vascularization, bioartificial organs, transplantation and functionality, cellular agriculture
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