Engineered extracellular vesicle-encapsulated CHIP as novel nanotherapeutics for treatment of renal fibrosis.

Abstract

Renal interstitial fibrosis (RIF) is a fundamental pathological feature of chronic kidney disease (CKD). However, toxicity and poor renal enrichment of fibrosis inhibitors limit their further applications. In this study, a platform for CKD therapy is developed using superparamagnetic iron oxide nanoparticles (SPION) decorated mesenchymal stem cells derived extracellular vesicles with carboxyl terminus of Hsc70-interacting protein (CHIP) high expression (SPION-EVs) to achieve higher renal-targeting antifibrotic therapeutic effect. SPION-EVs selectively accumulate at the injury renal sites under an external magnetic field. Moreover, SPION-EVs deliver CHIP to induce Smad2/3 degradation in renal tubular cells which alleviates Smad2/3 activation-mediated fibrosis-like changes and collagen deposition. The extracellular vesicle engineering technology provides a potential nanoplatform for RIF therapy through CHIP-mediated Smad2/3 degradation.

• Authors: Cheng Ji, Jiahui Zhang, Linru Shi, Hui Shi, Wenrong Xu, Jianhua Jin, Hui Qian
• Journal: NPJ Regenerative medicine (NPJ Regen Med) Vol. 9 Issue 1 Pg. 3 (Jan 13 2024) ISSN: 2057-3995 [Electronic] United States
• PMID: 38218925 (Publication Type: Journal Article)
• Copyright: © 2024. The Author(s).