Enhanced glomerular transfection by BMP7 gene nanocarriers inhibits CKD and promotes SOX9-dependent tubule regeneration

IF 13.2 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Nano Today Pub Date : 2024-11-04 DOI:10.1016/j.nantod.2024.102545
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
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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.
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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
肾脏纤维化和肾功能丧失是慢性肾脏病(CKD)的主要特征。为了解决缺乏有效治疗方法的问题,研究人员制备了多功能逐层(LbL)组装聚合物基因载体纳米颗粒(PCHS-NP),以实现在肾小球细胞内的优先积聚和保留,从而有效利用皮质局部结构合成和旁分泌抗纤维化生长因子骨形态发生蛋白-7(BMP7)。PCHS-NP 具有稳定的均质形态、肾脏靶向功能、抗氧化作用和高转染效率。在单侧输尿管梗阻(UUO)诱导的肾脏纤维化中,单次全身注射PCHS-NP可防止肾小管萎缩和间质纤维化,由此产生的组织微环境更有利于表达SOX9的增殖性肾小管细胞上调所驱动的肾小管再生。在长期叶酸(FA)诱导的肾脏纤维化中,我们发现早期、晚期和重复全身注射叶酸都能恢复肾脏的健康和功能。这项研究表明,PCHS-NP是治疗慢性肾功能衰竭的一种很有前景的治疗方案。
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来源期刊
Nano Today
Nano Today 工程技术-材料科学:综合
CiteScore
21.50
自引率
3.40%
发文量
305
审稿时长
40 days
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.
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