Antifibrotic Effects of Tetrahedral Framework Nucleic Acids by Inhibiting Macrophage Polarization and Macrophage-myofibroblast Transition in Bladder Remodeling.

Bladder outlet obstruction (BOO) is a prevalent condition arising from urethral stricture, posterior urethral valves and benign prostatic hyperplasia. Long-term obstruction can lead to bladder remodeling, which is characterized by inflammatory cell infiltration, detrusor hypertrophy and fibrosis. Until now, there have been no efficacious therapeutic options for BOO-induced remodeling. Tetrahedral framework nucleic acids (tFNAs) are a type of novel three-dimensional DNA nanomaterial that possesses excellent antifibrotic effects. Here, we aimed to determine the treatment effects of tFNAs on BOO-induced remodeling. Four single-strand DNAs were self-assembled to form tetrahedral framework DNA nanostructures, and the antifibrotic effects of tFNAs were investigated in an in vivo BOO animal model and an in vitro transforming growth factor beta1 (TGF-β1)-induced fibrosis model. The results demonstrated that tFNAs could ameliorate BOO-induced bladder fibrosis and dysfunction by inhibiting M2 macrophage polarization and the macrophage-myofibroblast transition (MMT) process. Furthermore, tFNAs regulate M2 polarization and the MMT process by deactivating the signal transducer and activator of transcription (Stat) and TGF-β1/small mothers against decapentaplegic (Smad) pathways, respectively. This is the first study to reveal that tFNAs might be a promising nanomaterial for the treatment of BOO-induced remodeling. This article is protected by copyright. All rights reserved.