Engineered Exosomes Carrying Super-Repressor IκB Reduced Biliary Atresia-Induced Liver Fibrosis in Minipig and Mouse Models
<b>Background and Aim:</b> Biliary atresia is a rare, progressive disease that affects the bile ducts in newborns. Persistent bile duct obstruction induces various pathological conditions, including jaundice, inflammation, and liver fibrosis; however, the exact pathogenesis of biliary at...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-02-01
|
| Series: | Pharmaceutics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4923/17/2/264 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850080588276432896 |
|---|---|
| author | Jisoo Kang Cheolhyoung Park Hanoul Yun Chulhee Choi Wonhyo Seo |
| author_facet | Jisoo Kang Cheolhyoung Park Hanoul Yun Chulhee Choi Wonhyo Seo |
| author_sort | Jisoo Kang |
| collection | DOAJ |
| description | <b>Background and Aim:</b> Biliary atresia is a rare, progressive disease that affects the bile ducts in newborns. Persistent bile duct obstruction induces various pathological conditions, including jaundice, inflammation, and liver fibrosis; however, the exact pathogenesis of biliary atresia is not yet fully understood. Nuclear factor-κB (NF-κB) is widely acknowledged as a key regulator in the pathogenesis of hepatitis and liver fibrosis, and extensive research has been conducted to develop strategies to effectively inhibit its activity to mitigate liver damage. Exosome-based therapeutic platforms offer targeted NF-κB inhibition with low immunogenicity and enhanced liver-specific delivery. This study aimed to evaluate the therapeutic efficacy of Exo-SrIκB in treating cholestatic liver fibrosis using experimental animal models. <b>Methods:</b> Exo-SrIκB (an exosome-based therapy containing the super-repressor IκB protein) using EXPLOR technology (Exosome engineering for Protein Loading via Optically Reversible protein-protein interactions) to encapsulate the super repressor IκB (SrIκB) within exosomes. The therapeutic efficacy of Exo-SrIκB was assessed in minipig and mouse models with experimentally induced cholestatic liver disease. <b>Results:</b> Administration of Exo-SrIκB significantly attenuated liver fibrosis progression in both animal models by inhibiting NF-κB nuclear translocation and reducing the expression of fibrotic markers. Treated animals exhibited reduced collagen deposition, lower α-SMA levels, and improved hepatic function compared to untreated controls. <b>Conclusion:</b> Exo-SrIκB effectively suppressed NF-κB signaling and alleviated liver fibrosis in experimental cholestatic liver disease models, suggesting that exosome-based therapeutics may offer a targeted and biocompatible application to managing liver fibrosis and other chronic liver diseases. |
| format | Article |
| id | doaj-art-272e34d538404d43b9cbd530917a0494 |
| institution | DOAJ |
| issn | 1999-4923 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj-art-272e34d538404d43b9cbd530917a04942025-08-20T02:44:54ZengMDPI AGPharmaceutics1999-49232025-02-0117226410.3390/pharmaceutics17020264Engineered Exosomes Carrying Super-Repressor IκB Reduced Biliary Atresia-Induced Liver Fibrosis in Minipig and Mouse ModelsJisoo Kang0Cheolhyoung Park1Hanoul Yun2Chulhee Choi3Wonhyo Seo4College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 03760, Republic of KoreaILIAS Biologics Inc., Daejeon 34014, Republic of KoreaILIAS Biologics Inc., Daejeon 34014, Republic of KoreaILIAS Biologics Inc., Daejeon 34014, Republic of KoreaCollege of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 03760, Republic of Korea<b>Background and Aim:</b> Biliary atresia is a rare, progressive disease that affects the bile ducts in newborns. Persistent bile duct obstruction induces various pathological conditions, including jaundice, inflammation, and liver fibrosis; however, the exact pathogenesis of biliary atresia is not yet fully understood. Nuclear factor-κB (NF-κB) is widely acknowledged as a key regulator in the pathogenesis of hepatitis and liver fibrosis, and extensive research has been conducted to develop strategies to effectively inhibit its activity to mitigate liver damage. Exosome-based therapeutic platforms offer targeted NF-κB inhibition with low immunogenicity and enhanced liver-specific delivery. This study aimed to evaluate the therapeutic efficacy of Exo-SrIκB in treating cholestatic liver fibrosis using experimental animal models. <b>Methods:</b> Exo-SrIκB (an exosome-based therapy containing the super-repressor IκB protein) using EXPLOR technology (Exosome engineering for Protein Loading via Optically Reversible protein-protein interactions) to encapsulate the super repressor IκB (SrIκB) within exosomes. The therapeutic efficacy of Exo-SrIκB was assessed in minipig and mouse models with experimentally induced cholestatic liver disease. <b>Results:</b> Administration of Exo-SrIκB significantly attenuated liver fibrosis progression in both animal models by inhibiting NF-κB nuclear translocation and reducing the expression of fibrotic markers. Treated animals exhibited reduced collagen deposition, lower α-SMA levels, and improved hepatic function compared to untreated controls. <b>Conclusion:</b> Exo-SrIκB effectively suppressed NF-κB signaling and alleviated liver fibrosis in experimental cholestatic liver disease models, suggesting that exosome-based therapeutics may offer a targeted and biocompatible application to managing liver fibrosis and other chronic liver diseases.https://www.mdpi.com/1999-4923/17/2/264biliary atresialiver fibrosisengineered exosomesuper-repressor IκB |
| spellingShingle | Jisoo Kang Cheolhyoung Park Hanoul Yun Chulhee Choi Wonhyo Seo Engineered Exosomes Carrying Super-Repressor IκB Reduced Biliary Atresia-Induced Liver Fibrosis in Minipig and Mouse Models Pharmaceutics biliary atresia liver fibrosis engineered exosome super-repressor IκB |
| title | Engineered Exosomes Carrying Super-Repressor IκB Reduced Biliary Atresia-Induced Liver Fibrosis in Minipig and Mouse Models |
| title_full | Engineered Exosomes Carrying Super-Repressor IκB Reduced Biliary Atresia-Induced Liver Fibrosis in Minipig and Mouse Models |
| title_fullStr | Engineered Exosomes Carrying Super-Repressor IκB Reduced Biliary Atresia-Induced Liver Fibrosis in Minipig and Mouse Models |
| title_full_unstemmed | Engineered Exosomes Carrying Super-Repressor IκB Reduced Biliary Atresia-Induced Liver Fibrosis in Minipig and Mouse Models |
| title_short | Engineered Exosomes Carrying Super-Repressor IκB Reduced Biliary Atresia-Induced Liver Fibrosis in Minipig and Mouse Models |
| title_sort | engineered exosomes carrying super repressor iκb reduced biliary atresia induced liver fibrosis in minipig and mouse models |
| topic | biliary atresia liver fibrosis engineered exosome super-repressor IκB |
| url | https://www.mdpi.com/1999-4923/17/2/264 |
| work_keys_str_mv | AT jisookang engineeredexosomescarryingsuperrepressorikbreducedbiliaryatresiainducedliverfibrosisinminipigandmousemodels AT cheolhyoungpark engineeredexosomescarryingsuperrepressorikbreducedbiliaryatresiainducedliverfibrosisinminipigandmousemodels AT hanoulyun engineeredexosomescarryingsuperrepressorikbreducedbiliaryatresiainducedliverfibrosisinminipigandmousemodels AT chulheechoi engineeredexosomescarryingsuperrepressorikbreducedbiliaryatresiainducedliverfibrosisinminipigandmousemodels AT wonhyoseo engineeredexosomescarryingsuperrepressorikbreducedbiliaryatresiainducedliverfibrosisinminipigandmousemodels |