{"title":"Enhanced glomerular transfection by BMP7 gene nanocarriers inhibits CKD and promotes SOX9-dependent tubule regeneration","authors":"","doi":"10.1016/j.nantod.2024.102545","DOIUrl":null,"url":null,"abstract":"<div><div>Renal fibrosis and loss of kidney function are key characteristics of chronic kidney disease (CKD). To address the lack of effective treatments, multifunctional layer-by-layer (LbL) assembled polymeric gene-carrier nanoparticles (PCHS-NP) are prepared to realize preferential accumulation and retention within renal glomerular cells, thereby effectively leveraging cortically localized structures for the synthesis and paracrine secretion of the antifibrotic growth factor, bone morphogenetic protein-7 (BMP7). PCHS-NP had stable homogenous morphologies, kidney-targeting functionality, antioxidative effects, and high transfection efficiency. In unilateral ureteral obstruction (UUO)-induced renal fibrosis, a single systemic injection of PCHS-NP prevents tubular atrophy and interstitial fibrosis, and the resultant tissue microenvironment is more conducive to tubular regeneration driven by the upregulation of proliferative SOX9-expressing tubular cells. In longer-term folic acid (FA)-induced renal fibrosis, we show that early, late, and repeat systemic injections restore kidney health and function. This study indicates that PCHS-NP accomplish a promising therapeutic option for the treatment of CKD.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":null,"pages":null},"PeriodicalIF":13.2000,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nano Today","FirstCategoryId":"88","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1748013224004018","RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
Abstract
Renal fibrosis and loss of kidney function are key characteristics of chronic kidney disease (CKD). To address the lack of effective treatments, multifunctional layer-by-layer (LbL) assembled polymeric gene-carrier nanoparticles (PCHS-NP) are prepared to realize preferential accumulation and retention within renal glomerular cells, thereby effectively leveraging cortically localized structures for the synthesis and paracrine secretion of the antifibrotic growth factor, bone morphogenetic protein-7 (BMP7). PCHS-NP had stable homogenous morphologies, kidney-targeting functionality, antioxidative effects, and high transfection efficiency. In unilateral ureteral obstruction (UUO)-induced renal fibrosis, a single systemic injection of PCHS-NP prevents tubular atrophy and interstitial fibrosis, and the resultant tissue microenvironment is more conducive to tubular regeneration driven by the upregulation of proliferative SOX9-expressing tubular cells. In longer-term folic acid (FA)-induced renal fibrosis, we show that early, late, and repeat systemic injections restore kidney health and function. This study indicates that PCHS-NP accomplish a promising therapeutic option for the treatment of CKD.
期刊介绍:
Nano Today is a journal dedicated to publishing influential and innovative work in the field of nanoscience and technology. It covers a wide range of subject areas including biomaterials, materials chemistry, materials science, chemistry, bioengineering, biochemistry, genetics and molecular biology, engineering, and nanotechnology. The journal considers articles that inform readers about the latest research, breakthroughs, and topical issues in these fields. It provides comprehensive coverage through a mixture of peer-reviewed articles, research news, and information on key developments. Nano Today is abstracted and indexed in Science Citation Index, Ei Compendex, Embase, Scopus, and INSPEC.