Yifan Tai , Zhen Liu , Yanrong Wang , Xinyan Zhang , Ruifang Li , Jiangyue Yu , Yao Chen , Lili Zhao , Jia Li , Xueyuan Bai , Deling Kong , Adam C. Midgley
{"title":"通过 BMP7 基因纳米载体增强肾小球转染可抑制 CKD 并促进 SOX9 依赖性肾小管再生","authors":"Yifan Tai , Zhen Liu , Yanrong Wang , Xinyan Zhang , Ruifang Li , Jiangyue Yu , Yao Chen , Lili Zhao , Jia Li , Xueyuan Bai , Deling Kong , Adam C. Midgley","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":"59 ","pages":"Article 102545"},"PeriodicalIF":13.2000,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Enhanced glomerular transfection by BMP7 gene nanocarriers inhibits CKD and promotes SOX9-dependent tubule regeneration\",\"authors\":\"Yifan Tai , Zhen Liu , Yanrong Wang , Xinyan Zhang , Ruifang Li , Jiangyue Yu , Yao Chen , Lili Zhao , Jia Li , Xueyuan Bai , Deling Kong , Adam C. Midgley\",\"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\":\"59 \",\"pages\":\"Article 102545\"},\"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}","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}
Enhanced glomerular transfection by BMP7 gene nanocarriers inhibits CKD and promotes SOX9-dependent tubule regeneration
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.