Extended-release of therapeutic microRNA via a host-guest supramolecular hydrogel to locally alleviate renal interstitial fibrosis.

Abstract

Activated fibroblasts are critical contributors to renal interstitial fibrosis thus becoming the cellular target for fibrosis treatment. Previously, microRNA 29 b (miR-29 b) is shown to be down-regulated in various animal models of renal fibrosis. Herein, we describe a facile strategy to achieve localized and sustained delivery of therapeutic microRNA to the kidney via a host-guest supramolecular hydrogel. Specifically, cationic bovine serum albumin is used to complex with miR-29 b to afford nanocomplexes (cBSA/miR-29 b), which is proven to specifically inhibit fibroblast activation in a dose-dependent manner in vitro. Following unilateral ureteral obstruction in mice, a single injection of the hydrogel loaded with cBSA/miR-29 b in vivo, significantly down-regulated proteins and genes related to fibrosis for up to 21 days without affecting the normal liver or kidney functions. Overall, the localized delivery of cBSA/miR-29 b via a host-guest supramolecular hydrogel represents a safe and effective intervention strategy to delay and reverse the progression of interstitial renal fibrosis.