Quercetin nanoformulation-embedded hydrogel inhibits osteopontin mediated ferroptosis for intervertebral disc degeneration alleviation
Abstract Reactive oxygen species (ROS) play a pivotal role in multiple events during the progression of intervertebral disc degeneration (IDD). Hence, the precision treatment targets associated with ROS should be further explored to promote developing effective therapeutic strategies. In this study,...
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BMC
2025-07-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-025-03574-w |
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| author | Jitian Li Lemeng Ren Lei Wan Man Liu Mingyu Zhao Yazhou Lin Jiancheng Zheng Yun Tang Yage Luo Yan Ma Lei Wang Peng Cao Zhe Chen Wenjie Ren Fei Wang |
| author_facet | Jitian Li Lemeng Ren Lei Wan Man Liu Mingyu Zhao Yazhou Lin Jiancheng Zheng Yun Tang Yage Luo Yan Ma Lei Wang Peng Cao Zhe Chen Wenjie Ren Fei Wang |
| author_sort | Jitian Li |
| collection | DOAJ |
| description | Abstract Reactive oxygen species (ROS) play a pivotal role in multiple events during the progression of intervertebral disc degeneration (IDD). Hence, the precision treatment targets associated with ROS should be further explored to promote developing effective therapeutic strategies. In this study, by analyzing specimens from patients and RNA sequencing of ROS-induced human primary nucleus pulposus cells (NPCs), osteopontin (OPN) and ferroptosis were identified as critical molecular entities and cellular pathways implicated in ROS-mediated IDD. Subsequent animal models and cellular assays determined that ROS induced upregulation of OPN, which in turn triggered ferroptosis in NPCs and intervertebral discs, consequently leading to IDD. Building upon these findings, a comprehensive screening of molecular drug database revealed that quercetin, an antioxidant molecule compound, possesses the capacity to couple OPN, thereby mitigating OPN-induced ferroptosis and IDD. In addition, the compound of quercetin for targeting OPN was encapsulated in phenylboric acid modified dendrimer (G3-PBA) nanoparticles to improve its solubility, and then embedded in a ROS-degradable and injectable hydrogel, thereby achieving on-demand release of quercetin with the progression of IDD. Collectively, this study not only identified a novel therapeutic target, but also engineered an effective therapeutic strategy intended for the autonomous management of IDD. Graphical abstract |
| format | Article |
| id | doaj-art-3aeb2327477f4cf2840b27cbccd78cb3 |
| institution | Kabale University |
| issn | 1477-3155 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj-art-3aeb2327477f4cf2840b27cbccd78cb32025-08-20T03:46:27ZengBMCJournal of Nanobiotechnology1477-31552025-07-0123111710.1186/s12951-025-03574-wQuercetin nanoformulation-embedded hydrogel inhibits osteopontin mediated ferroptosis for intervertebral disc degeneration alleviationJitian Li0Lemeng Ren1Lei Wan2Man Liu3Mingyu Zhao4Yazhou Lin5Jiancheng Zheng6Yun Tang7Yage Luo8Yan Ma9Lei Wang10Peng Cao11Zhe Chen12Wenjie Ren13Fei Wang14The Third Affiliated Hospital of Xinxiang Medical University, Clinical Medical Center of Tissue Engineering and Regeneration, Zhongyuan Regenerative Medicine Laboratory, Xinxiang Medical UniversityDepartment of Orthopedics, Ruijin Hospital, Shanghai Jiaotong University School of MedicineDepartment of Osteology, The Second Affiliated Hospital of Luohe Medical CollegeLaboratory of Molecular Biology, Luoyang Orthopedic Hospital of Henan Province (Orthopedic Hospital of Henan Province), Henan University of Chinese MedicineLaboratory of Molecular Biology, Luoyang Orthopedic Hospital of Henan Province (Orthopedic Hospital of Henan Province), Henan University of Chinese MedicineDepartment of Orthopedics, Ruijin Hospital, Shanghai Jiaotong University School of MedicineDepartment of Orthopedics, Ruijin Hospital, Shanghai Jiaotong University School of MedicineDepartment of Orthopedics, Ruijin Hospital, Shanghai Jiaotong University School of MedicineLaboratory of Molecular Biology, Luoyang Orthopedic Hospital of Henan Province (Orthopedic Hospital of Henan Province), Henan University of Chinese MedicineLaboratory of Molecular Biology, Luoyang Orthopedic Hospital of Henan Province (Orthopedic Hospital of Henan Province), Henan University of Chinese MedicineThe Third Affiliated Hospital of Xinxiang Medical University, Clinical Medical Center of Tissue Engineering and Regeneration, Zhongyuan Regenerative Medicine Laboratory, Xinxiang Medical UniversityDepartment of Orthopedics, Ruijin Hospital, Shanghai Jiaotong University School of MedicineDepartment of Orthopedics, Ruijin Hospital, Shanghai Jiaotong University School of MedicineThe Third Affiliated Hospital of Xinxiang Medical University, Clinical Medical Center of Tissue Engineering and Regeneration, Zhongyuan Regenerative Medicine Laboratory, Xinxiang Medical UniversityDepartment of Orthopedics, Ruijin Hospital, Shanghai Jiaotong University School of MedicineAbstract Reactive oxygen species (ROS) play a pivotal role in multiple events during the progression of intervertebral disc degeneration (IDD). Hence, the precision treatment targets associated with ROS should be further explored to promote developing effective therapeutic strategies. In this study, by analyzing specimens from patients and RNA sequencing of ROS-induced human primary nucleus pulposus cells (NPCs), osteopontin (OPN) and ferroptosis were identified as critical molecular entities and cellular pathways implicated in ROS-mediated IDD. Subsequent animal models and cellular assays determined that ROS induced upregulation of OPN, which in turn triggered ferroptosis in NPCs and intervertebral discs, consequently leading to IDD. Building upon these findings, a comprehensive screening of molecular drug database revealed that quercetin, an antioxidant molecule compound, possesses the capacity to couple OPN, thereby mitigating OPN-induced ferroptosis and IDD. In addition, the compound of quercetin for targeting OPN was encapsulated in phenylboric acid modified dendrimer (G3-PBA) nanoparticles to improve its solubility, and then embedded in a ROS-degradable and injectable hydrogel, thereby achieving on-demand release of quercetin with the progression of IDD. Collectively, this study not only identified a novel therapeutic target, but also engineered an effective therapeutic strategy intended for the autonomous management of IDD. Graphical abstracthttps://doi.org/10.1186/s12951-025-03574-wIntervertebral disc degenerationQuercetinOsteopontinFerroptosisInjectable hydrogel |
| spellingShingle | Jitian Li Lemeng Ren Lei Wan Man Liu Mingyu Zhao Yazhou Lin Jiancheng Zheng Yun Tang Yage Luo Yan Ma Lei Wang Peng Cao Zhe Chen Wenjie Ren Fei Wang Quercetin nanoformulation-embedded hydrogel inhibits osteopontin mediated ferroptosis for intervertebral disc degeneration alleviation Journal of Nanobiotechnology Intervertebral disc degeneration Quercetin Osteopontin Ferroptosis Injectable hydrogel |
| title | Quercetin nanoformulation-embedded hydrogel inhibits osteopontin mediated ferroptosis for intervertebral disc degeneration alleviation |
| title_full | Quercetin nanoformulation-embedded hydrogel inhibits osteopontin mediated ferroptosis for intervertebral disc degeneration alleviation |
| title_fullStr | Quercetin nanoformulation-embedded hydrogel inhibits osteopontin mediated ferroptosis for intervertebral disc degeneration alleviation |
| title_full_unstemmed | Quercetin nanoformulation-embedded hydrogel inhibits osteopontin mediated ferroptosis for intervertebral disc degeneration alleviation |
| title_short | Quercetin nanoformulation-embedded hydrogel inhibits osteopontin mediated ferroptosis for intervertebral disc degeneration alleviation |
| title_sort | quercetin nanoformulation embedded hydrogel inhibits osteopontin mediated ferroptosis for intervertebral disc degeneration alleviation |
| topic | Intervertebral disc degeneration Quercetin Osteopontin Ferroptosis Injectable hydrogel |
| url | https://doi.org/10.1186/s12951-025-03574-w |
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