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.

Engineered Extracellular Vesicles in Chronic Kidney Diseases: A Comprehensive Review

“… 89 For instance, Ji et al introduced a new approach for treating CKD by using superparamagnetic iron oxide nanoparticles (SPION)-decorated MSCs-derived EVs with high expression of carboxyl terminus of Hsc70-interacting protein (CHIP), which selectively target injured renal sites under a magnetic field and deliver CHIP to alleviate fibrosis, offering a promising nanoplatform for CKD therapy ( Figure 5 ). 90

Figure 5 MSC-EVs-CHIP alleviate fibrosis through CHIP delivery. ( A ) TEM images: MSC-EVs and MSC-EVs-CHIP.

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“…89 For instance, Ji et al introduced a new approach for treating CKD by using superparamagnetic iron oxide nanoparticles (SPION)-decorated MSCs-derived EVs with high expression of carboxyl terminus of Hsc70-interacting protein (CHIP), which selectively target injured renal sites under a magnetic field and deliver CHIP to alleviate fibrosis, offering a promising nanoplatform for CKD therapy (Figure 5). 90 In summary, engineered EVs have renoprotective effects by reducing renal fibrosis, and offering targeted treatment strategies. These findings suggest a potential paradigm shift in CKD management towards personalized and effective therapeutic interventions utilizing EV-based approaches.…”