Sequentially assembled co-delivery nanoplatform of SIRT1 protein and SOX9-expressing plasmid for multipronged therapy of intervertebral disc degeneration
Abstract Nucleus pulposus cells (NPCs) undergo metabolic disorders and matrix pathological remodeling under the influence of various adverse factors during intervertebral disc degeneration (IVDD), whereas post-translational modifications (PTMs) can confer cells with the capacity to respond quickly a...
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2025-05-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-025-03401-2 |
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| author | Xiaoyu Zhang Qianping Guo Jiawei Fang Qi Cheng Zhuang Zhu Qifan Yu Huan Wang Youzhi Hong Chengyuan Liu Huilin Yang Caihong Zhu Bin Li Li Ni |
| author_facet | Xiaoyu Zhang Qianping Guo Jiawei Fang Qi Cheng Zhuang Zhu Qifan Yu Huan Wang Youzhi Hong Chengyuan Liu Huilin Yang Caihong Zhu Bin Li Li Ni |
| author_sort | Xiaoyu Zhang |
| collection | DOAJ |
| description | Abstract Nucleus pulposus cells (NPCs) undergo metabolic disorders and matrix pathological remodeling under the influence of various adverse factors during intervertebral disc degeneration (IVDD), whereas post-translational modifications (PTMs) can confer cells with the capacity to respond quickly and adapt to complex environmental changes. Here, SIRT1 protein, a key regulator within PTMs framework, was applied against the hostile degenerative microenvironment. Then, it was sequentially assembled with SOX9-expressing plasmid, an essential transcription factor to promote extracellular matrix (ECM) biosynthesis, onto a phenylboronic acid-functionalized G5-dendrimer to construct a multifunctional nanoplatform for IVDD therapy. In vitro, the nanoplatforms showed antioxidant capacity, and the ability to restore mitochondrial homeostasis and normal ECM metabolism, as well as to maintain cellular phenotypes. RNA sequencing suggested that inhibition of the Nod-like receptor signaling might be the mechanism behind their therapeutic effects. The nanoplatforms were then wrapped in a designed dynamic hydrogel, not only prolonging the retention time of the loaded cargoes, but also well maintaining the disc structure, height, and water content in vivo. Overall, this study presents a convenient assembled strategy to inhibit the multiple adverse factors, and hold promise for the IVDD treatment. Graphical abstract |
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| institution | OA Journals |
| issn | 1477-3155 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj-art-ca47cd0d34a64c7eb31a8cedc993d2ee2025-08-20T01:49:40ZengBMCJournal of Nanobiotechnology1477-31552025-05-0123112510.1186/s12951-025-03401-2Sequentially assembled co-delivery nanoplatform of SIRT1 protein and SOX9-expressing plasmid for multipronged therapy of intervertebral disc degenerationXiaoyu Zhang0Qianping Guo1Jiawei Fang2Qi Cheng3Zhuang Zhu4Qifan Yu5Huan Wang6Youzhi Hong7Chengyuan Liu8Huilin Yang9Caihong Zhu10Bin Li11Li Ni12Department of Orthopedic Surgery, Medical 3D Printing Center, The First Affiliated Hospital, Orthopedic Institute, School of Basic Medical Sciences, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Medical College, Soochow University, SuzhouDepartment of Orthopedic Surgery, Medical 3D Printing Center, The First Affiliated Hospital, Orthopedic Institute, School of Basic Medical Sciences, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Medical College, Soochow University, SuzhouDepartment of Orthopedic Surgery, Medical 3D Printing Center, The First Affiliated Hospital, Orthopedic Institute, School of Basic Medical Sciences, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Medical College, Soochow University, SuzhouDepartment of Orthopedic Surgery, Medical 3D Printing Center, The First Affiliated Hospital, Orthopedic Institute, School of Basic Medical Sciences, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Medical College, Soochow University, SuzhouDepartment of Orthopedic Surgery, Medical 3D Printing Center, The First Affiliated Hospital, Orthopedic Institute, School of Basic Medical Sciences, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Medical College, Soochow University, SuzhouDepartment of Orthopedic Surgery, Medical 3D Printing Center, The First Affiliated Hospital, Orthopedic Institute, School of Basic Medical Sciences, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Medical College, Soochow University, SuzhouDepartment of Orthopedic Surgery, Medical 3D Printing Center, The First Affiliated Hospital, Orthopedic Institute, School of Basic Medical Sciences, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Medical College, Soochow University, SuzhouDepartment of Orthopedic Surgery, Medical 3D Printing Center, The First Affiliated Hospital, Orthopedic Institute, School of Basic Medical Sciences, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Medical College, Soochow University, SuzhouDepartment of Orthopedic Surgery, Medical 3D Printing Center, The First Affiliated Hospital, Orthopedic Institute, School of Basic Medical Sciences, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Medical College, Soochow University, SuzhouDepartment of Orthopedic Surgery, Medical 3D Printing Center, The First Affiliated Hospital, Orthopedic Institute, School of Basic Medical Sciences, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Medical College, Soochow University, SuzhouDepartment of Orthopedic Surgery, Medical 3D Printing Center, The First Affiliated Hospital, Orthopedic Institute, School of Basic Medical Sciences, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Medical College, Soochow University, SuzhouDepartment of Orthopedic Surgery, Medical 3D Printing Center, The First Affiliated Hospital, Orthopedic Institute, School of Basic Medical Sciences, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Medical College, Soochow University, SuzhouDepartment of Orthopedic Surgery, Medical 3D Printing Center, The First Affiliated Hospital, Orthopedic Institute, School of Basic Medical Sciences, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Medical College, Soochow University, SuzhouAbstract Nucleus pulposus cells (NPCs) undergo metabolic disorders and matrix pathological remodeling under the influence of various adverse factors during intervertebral disc degeneration (IVDD), whereas post-translational modifications (PTMs) can confer cells with the capacity to respond quickly and adapt to complex environmental changes. Here, SIRT1 protein, a key regulator within PTMs framework, was applied against the hostile degenerative microenvironment. Then, it was sequentially assembled with SOX9-expressing plasmid, an essential transcription factor to promote extracellular matrix (ECM) biosynthesis, onto a phenylboronic acid-functionalized G5-dendrimer to construct a multifunctional nanoplatform for IVDD therapy. In vitro, the nanoplatforms showed antioxidant capacity, and the ability to restore mitochondrial homeostasis and normal ECM metabolism, as well as to maintain cellular phenotypes. RNA sequencing suggested that inhibition of the Nod-like receptor signaling might be the mechanism behind their therapeutic effects. The nanoplatforms were then wrapped in a designed dynamic hydrogel, not only prolonging the retention time of the loaded cargoes, but also well maintaining the disc structure, height, and water content in vivo. Overall, this study presents a convenient assembled strategy to inhibit the multiple adverse factors, and hold promise for the IVDD treatment. Graphical abstracthttps://doi.org/10.1186/s12951-025-03401-2Sequentially assembled nanoplatformCo-deliveryPost-translational modificationsMitochondrial homeostasisIntervertebral disc degeneration |
| spellingShingle | Xiaoyu Zhang Qianping Guo Jiawei Fang Qi Cheng Zhuang Zhu Qifan Yu Huan Wang Youzhi Hong Chengyuan Liu Huilin Yang Caihong Zhu Bin Li Li Ni Sequentially assembled co-delivery nanoplatform of SIRT1 protein and SOX9-expressing plasmid for multipronged therapy of intervertebral disc degeneration Journal of Nanobiotechnology Sequentially assembled nanoplatform Co-delivery Post-translational modifications Mitochondrial homeostasis Intervertebral disc degeneration |
| title | Sequentially assembled co-delivery nanoplatform of SIRT1 protein and SOX9-expressing plasmid for multipronged therapy of intervertebral disc degeneration |
| title_full | Sequentially assembled co-delivery nanoplatform of SIRT1 protein and SOX9-expressing plasmid for multipronged therapy of intervertebral disc degeneration |
| title_fullStr | Sequentially assembled co-delivery nanoplatform of SIRT1 protein and SOX9-expressing plasmid for multipronged therapy of intervertebral disc degeneration |
| title_full_unstemmed | Sequentially assembled co-delivery nanoplatform of SIRT1 protein and SOX9-expressing plasmid for multipronged therapy of intervertebral disc degeneration |
| title_short | Sequentially assembled co-delivery nanoplatform of SIRT1 protein and SOX9-expressing plasmid for multipronged therapy of intervertebral disc degeneration |
| title_sort | sequentially assembled co delivery nanoplatform of sirt1 protein and sox9 expressing plasmid for multipronged therapy of intervertebral disc degeneration |
| topic | Sequentially assembled nanoplatform Co-delivery Post-translational modifications Mitochondrial homeostasis Intervertebral disc degeneration |
| url | https://doi.org/10.1186/s12951-025-03401-2 |
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