Targeted glomerular mesangium transfection by antifibrotic gene nanocarriers inhibits kidney fibrosis and promotes regeneration

Abstract

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 the renal mesangium, thereby effectively leveraging cortically localized structures for the synthesis and paracrine secretion of the antifibrotic growth factor, bone morphogenetic protein-7 (BMP7). PCHS-NP have 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 repeat systemic injections restore kidney health and function. This study indicates that PCHS-NP accomplish a promising therapeutic option for the treatment of CKD.