High-density lipoprotein nanoparticles spontaneously target to damaged renal tubules and alleviate renal fibrosis by remodeling the fibrotic niches
Abstract Chronic kidney disease (CKD) ultimately causes renal fibrosis and end-stage renal disease, thus seriously threatens human health. However, current medications for CKD and fibrosis are inefficient, which is often due to poor targeting capability to renal tubule. In this study, we discover th...
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-56223-z |
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| author | Shanshan He Xiaoyang Li Yuanyuan He Ling Guo Yunzhou Dong Leilei Wang Lan Yang Lin Li Shiyun Huang Jiali Fu Qing Lin Zhirong Zhang Ling Zhang |
| author_facet | Shanshan He Xiaoyang Li Yuanyuan He Ling Guo Yunzhou Dong Leilei Wang Lan Yang Lin Li Shiyun Huang Jiali Fu Qing Lin Zhirong Zhang Ling Zhang |
| author_sort | Shanshan He |
| collection | DOAJ |
| description | Abstract Chronic kidney disease (CKD) ultimately causes renal fibrosis and end-stage renal disease, thus seriously threatens human health. However, current medications for CKD and fibrosis are inefficient, which is often due to poor targeting capability to renal tubule. In this study, we discover that biomimetic high-density lipoprotein (bHDL) lipid nanoparticles possess excellent targeting ability to injured tubular epithelial cells by kidney injury molecule-1(KIM-1) mediated internalization. Thus, we co-load anti-inflammatory drug triptolide (TP) and anti-fibrotic drug nintedanib (BIBF) on bHDL nanoparticles to treat CKD. Based on the targeted delivery and mutual enhancement of the efficacy of co-delivered drugs, the bHDL-based system effectively reduces kidney injury and alleviates renal fibrosis in different CKD mouse models. The mechanistic study shows that BIBF and TP synergistically remodel the fibrotic niches by decreasing inflammatory cytokines, limiting immune cell infiltration and inhibiting the activation of myofibroblasts. The bHDL vehicle also possesses high manufacturability, good safety and adequately reduces the toxicity of TP. Thus, this system is promising for the treatment of CKD and bHDL has good potential for delivering agents to damaged renal tubular epithelial cells. |
| format | Article |
| id | doaj-art-e43b2fab6b1a4856be3b46d09422462a |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-e43b2fab6b1a4856be3b46d09422462a2025-02-02T12:33:27ZengNature PortfolioNature Communications2041-17232025-01-0116112010.1038/s41467-025-56223-zHigh-density lipoprotein nanoparticles spontaneously target to damaged renal tubules and alleviate renal fibrosis by remodeling the fibrotic nichesShanshan He0Xiaoyang Li1Yuanyuan He2Ling Guo3Yunzhou Dong4Leilei Wang5Lan Yang6Lin Li7Shiyun Huang8Jiali Fu9Qing Lin10Zhirong Zhang11Ling Zhang12Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan UniversityKey Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan UniversityCollege of Polymer Science and Engineering, West China School of Public Health, Med-X center of materials, Sichuan UniversityNational Engineering Technology Research Center for Miao Medicine, Guizhou Engineering Technology Research Center for Processing and Preparation of Traditional Chinese Medicine and Ethnic Medicine, College of Pharmaceutical Sciences, Guizhou University of Traditional Chinese MedicineKey Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan UniversityKey Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan UniversityCollege of Polymer Science and Engineering, West China School of Public Health, Med-X center of materials, Sichuan UniversityCollege of Polymer Science and Engineering, West China School of Public Health, Med-X center of materials, Sichuan UniversityKey Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan UniversityKey Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan UniversityKey Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan UniversityKey Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan UniversityCollege of Polymer Science and Engineering, West China School of Public Health, Med-X center of materials, Sichuan UniversityAbstract Chronic kidney disease (CKD) ultimately causes renal fibrosis and end-stage renal disease, thus seriously threatens human health. However, current medications for CKD and fibrosis are inefficient, which is often due to poor targeting capability to renal tubule. In this study, we discover that biomimetic high-density lipoprotein (bHDL) lipid nanoparticles possess excellent targeting ability to injured tubular epithelial cells by kidney injury molecule-1(KIM-1) mediated internalization. Thus, we co-load anti-inflammatory drug triptolide (TP) and anti-fibrotic drug nintedanib (BIBF) on bHDL nanoparticles to treat CKD. Based on the targeted delivery and mutual enhancement of the efficacy of co-delivered drugs, the bHDL-based system effectively reduces kidney injury and alleviates renal fibrosis in different CKD mouse models. The mechanistic study shows that BIBF and TP synergistically remodel the fibrotic niches by decreasing inflammatory cytokines, limiting immune cell infiltration and inhibiting the activation of myofibroblasts. The bHDL vehicle also possesses high manufacturability, good safety and adequately reduces the toxicity of TP. Thus, this system is promising for the treatment of CKD and bHDL has good potential for delivering agents to damaged renal tubular epithelial cells.https://doi.org/10.1038/s41467-025-56223-z |
| spellingShingle | Shanshan He Xiaoyang Li Yuanyuan He Ling Guo Yunzhou Dong Leilei Wang Lan Yang Lin Li Shiyun Huang Jiali Fu Qing Lin Zhirong Zhang Ling Zhang High-density lipoprotein nanoparticles spontaneously target to damaged renal tubules and alleviate renal fibrosis by remodeling the fibrotic niches Nature Communications |
| title | High-density lipoprotein nanoparticles spontaneously target to damaged renal tubules and alleviate renal fibrosis by remodeling the fibrotic niches |
| title_full | High-density lipoprotein nanoparticles spontaneously target to damaged renal tubules and alleviate renal fibrosis by remodeling the fibrotic niches |
| title_fullStr | High-density lipoprotein nanoparticles spontaneously target to damaged renal tubules and alleviate renal fibrosis by remodeling the fibrotic niches |
| title_full_unstemmed | High-density lipoprotein nanoparticles spontaneously target to damaged renal tubules and alleviate renal fibrosis by remodeling the fibrotic niches |
| title_short | High-density lipoprotein nanoparticles spontaneously target to damaged renal tubules and alleviate renal fibrosis by remodeling the fibrotic niches |
| title_sort | high density lipoprotein nanoparticles spontaneously target to damaged renal tubules and alleviate renal fibrosis by remodeling the fibrotic niches |
| url | https://doi.org/10.1038/s41467-025-56223-z |
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