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

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, researchers from Jiangsu University have developed a platform for CKD therapyusing 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.

Schematic illustrations of engineered extracellular vesicle
as novel nanotherapeutics against renal fibrosis

Fig. 7

A platform for RIF therapy using SPION decorate nanosized mesenchymal stem cells-derived extracellular vesicles with carboxyl terminus of Hsc70-interacting protein (CHIP) high-expression (SPION-EVs) is developed. SPION-EVs significantly enrichment of renal injury sites and induces Smad2/3 degradation of renal tubular cells, which alleviates fibrosis and inflammation, accompanying with rescued collagen deposition in RIF.

Ji C, Zhang J, Shi L, Shi H, Xu W, Jin J, Qian H. (2024) Engineered extracellular vesicle-encapsulated CHIP as novel nanotherapeutics for treatment of renal fibrosis. NPJ Regen Med 9(1):3. [article]

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