Engineering antioxidant ceria-zirconia nanomedicines for alleviating podocyte injury in rats with adriamycin-induced nephrotic syndrome
Abstract Background Primary nephrotic syndrome (PNS) is characterized by edema, heavy proteinuria, hypoalbuminemia and hyperlipidemia. Moreover, podocyte injury is the key pathological change of PNS. Even though the pathophysiological etiology of PNS has not been fully understood, the production of...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2023-10-01
|
| Series: | Journal of Nanobiotechnology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12951-023-02136-2 |
| _version_ | 1797451596137758720 |
|---|---|
| author | Lili Liu Meiqi Chang Rong Yang Li Ding Yu Chen Yulin Kang |
| author_facet | Lili Liu Meiqi Chang Rong Yang Li Ding Yu Chen Yulin Kang |
| author_sort | Lili Liu |
| collection | DOAJ |
| description | Abstract Background Primary nephrotic syndrome (PNS) is characterized by edema, heavy proteinuria, hypoalbuminemia and hyperlipidemia. Moreover, podocyte injury is the key pathological change of PNS. Even though the pathophysiological etiology of PNS has not been fully understood, the production of excessive reactive oxygen species (ROS) plays an important role in the development and progression of the disease. Glucocorticoids are the first-line medications for patients with PNS, but their clinical use is hampered by dose-dependent side effects. Herein, we accelerated the rate of conversion from Ce4+ to Ce3+ by doping Zr4+ in ceria-zirconia nanomedicines to treat the PNS rat model by removal of ROS. Results The engineered Ce0.7Zr0.3O2 (7CZ) nanomedicines significantly improved the ROS scavenging ability of podocytes at a very low dose, enabling effective inhibition of podocyte apoptosis and actin cytoskeleton depolymerization induced by adriamycin (ADR). Accordingly, podocyte injury was effectively alleviated in rat models of ADR-induced nephrotic syndrome, as confirmed by serum tests and renal tissue staining. Moreover, the mRNA sequencing assay revealed the protective molecular signaling pathways of 7CZ nanomedicines in podocytes. Conclusion 7CZ nanomedicines were highly effective in protecting against ADR-induced podocyte injury in vitro and in vivo at a very low concentration. Graphical Abstract |
| first_indexed | 2024-03-09T14:56:56Z |
| format | Article |
| id | doaj.art-385287ebf408478ba5b6fc97c5054ca8 |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-03-09T14:56:56Z |
| publishDate | 2023-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-385287ebf408478ba5b6fc97c5054ca82023-11-26T14:07:55ZengBMCJournal of Nanobiotechnology1477-31552023-10-0121111710.1186/s12951-023-02136-2Engineering antioxidant ceria-zirconia nanomedicines for alleviating podocyte injury in rats with adriamycin-induced nephrotic syndromeLili Liu0Meiqi Chang1Rong Yang2Li Ding3Yu Chen4Yulin Kang5School of Medicine, Anhui University of Science and TechnologyLaboratory Center, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese MedicineDepartment of Pediatrics, Shanghai Tenth People’s Hospital, School of Medicine, Tongji UniversityDepartment of Medical Ultrasound, National Clinical Research Center of Interventional Medicine, Shanghai Tenth People’s Hospital, Tongji University Cancer Center, Tongji University School of Medicine, Tongji UniversityMaterdicine Lab, School of Life Sciences, Shanghai UniversityDepartment of Nephrology and Rheumatology, Shanghai Children’s Hospital, School of Medicine, Shanghai Jiao Tong UniversityAbstract Background Primary nephrotic syndrome (PNS) is characterized by edema, heavy proteinuria, hypoalbuminemia and hyperlipidemia. Moreover, podocyte injury is the key pathological change of PNS. Even though the pathophysiological etiology of PNS has not been fully understood, the production of excessive reactive oxygen species (ROS) plays an important role in the development and progression of the disease. Glucocorticoids are the first-line medications for patients with PNS, but their clinical use is hampered by dose-dependent side effects. Herein, we accelerated the rate of conversion from Ce4+ to Ce3+ by doping Zr4+ in ceria-zirconia nanomedicines to treat the PNS rat model by removal of ROS. Results The engineered Ce0.7Zr0.3O2 (7CZ) nanomedicines significantly improved the ROS scavenging ability of podocytes at a very low dose, enabling effective inhibition of podocyte apoptosis and actin cytoskeleton depolymerization induced by adriamycin (ADR). Accordingly, podocyte injury was effectively alleviated in rat models of ADR-induced nephrotic syndrome, as confirmed by serum tests and renal tissue staining. Moreover, the mRNA sequencing assay revealed the protective molecular signaling pathways of 7CZ nanomedicines in podocytes. Conclusion 7CZ nanomedicines were highly effective in protecting against ADR-induced podocyte injury in vitro and in vivo at a very low concentration. Graphical Abstracthttps://doi.org/10.1186/s12951-023-02136-2Reactive oxygen speciesCeria-zirconia nanoparticlesPrimary nephrotic syndromePodocyte |
| spellingShingle | Lili Liu Meiqi Chang Rong Yang Li Ding Yu Chen Yulin Kang Engineering antioxidant ceria-zirconia nanomedicines for alleviating podocyte injury in rats with adriamycin-induced nephrotic syndrome Journal of Nanobiotechnology Reactive oxygen species Ceria-zirconia nanoparticles Primary nephrotic syndrome Podocyte |
| title | Engineering antioxidant ceria-zirconia nanomedicines for alleviating podocyte injury in rats with adriamycin-induced nephrotic syndrome |
| title_full | Engineering antioxidant ceria-zirconia nanomedicines for alleviating podocyte injury in rats with adriamycin-induced nephrotic syndrome |
| title_fullStr | Engineering antioxidant ceria-zirconia nanomedicines for alleviating podocyte injury in rats with adriamycin-induced nephrotic syndrome |
| title_full_unstemmed | Engineering antioxidant ceria-zirconia nanomedicines for alleviating podocyte injury in rats with adriamycin-induced nephrotic syndrome |
| title_short | Engineering antioxidant ceria-zirconia nanomedicines for alleviating podocyte injury in rats with adriamycin-induced nephrotic syndrome |
| title_sort | engineering antioxidant ceria zirconia nanomedicines for alleviating podocyte injury in rats with adriamycin induced nephrotic syndrome |
| topic | Reactive oxygen species Ceria-zirconia nanoparticles Primary nephrotic syndrome Podocyte |
| url | https://doi.org/10.1186/s12951-023-02136-2 |
| work_keys_str_mv | AT lililiu engineeringantioxidantceriazirconiananomedicinesforalleviatingpodocyteinjuryinratswithadriamycininducednephroticsyndrome AT meiqichang engineeringantioxidantceriazirconiananomedicinesforalleviatingpodocyteinjuryinratswithadriamycininducednephroticsyndrome AT rongyang engineeringantioxidantceriazirconiananomedicinesforalleviatingpodocyteinjuryinratswithadriamycininducednephroticsyndrome AT liding engineeringantioxidantceriazirconiananomedicinesforalleviatingpodocyteinjuryinratswithadriamycininducednephroticsyndrome AT yuchen engineeringantioxidantceriazirconiananomedicinesforalleviatingpodocyteinjuryinratswithadriamycininducednephroticsyndrome AT yulinkang engineeringantioxidantceriazirconiananomedicinesforalleviatingpodocyteinjuryinratswithadriamycininducednephroticsyndrome |