Methylprednisolone substituted lipid nanoparticles deliver C3 transferase mRNA for combined treatment of spinal cord injury
Abstract Spinal cord injury (SCI), characterized by the disruption of neural pathways and an increase in inflammatory cell infiltration, leads to profound and lasting neurological deficits, with a high risk of resulting in permanent disability. Currently, the therapeutic landscape for SCI is notably...
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BMC
2025-02-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-025-03153-z |
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| author | Haoru Dong Zongxing He Shiyi Cai Haiqiang Ma Lili Su Jianfeng Li Huiying Yang Rong Xie |
| author_facet | Haoru Dong Zongxing He Shiyi Cai Haiqiang Ma Lili Su Jianfeng Li Huiying Yang Rong Xie |
| author_sort | Haoru Dong |
| collection | DOAJ |
| description | Abstract Spinal cord injury (SCI), characterized by the disruption of neural pathways and an increase in inflammatory cell infiltration, leads to profound and lasting neurological deficits, with a high risk of resulting in permanent disability. Currently, the therapeutic landscape for SCI is notably sparse, with limited effective treatment options available. Methylprednisolone (MP), a widely used clinical anti-inflammatory agent for SCI, requires administration in high doses that are associated with significant adverse effects. In this study, we introduce an innovative approach by substituting cholesterol with MP to engineer a novel Lipid Nanoparticle (MP-LNP). This strategy aims to enhance the localization and concentration of MP at the injury site, thereby amplifying its therapeutic efficacy while mitigating systemic side effects. Furthermore, we explore the integration of C3 transferase mRNA into MP-LNPs. C3 transferase, a potent inhibitor of the RhoA pathway, has shown promise in facilitating neurological recovery in animal models of SCI and is currently being evaluated in clinical trials. The novel formulation, MP-LNP-C3, is designed for direct administration to the injury site during decompression surgery, offering a targeted therapeutic modality for SCI. Our findings reveal several significant advantages of this approach: Firstly, the incorporation of C3 transferase mRNA into MP-LNPs does not compromise the structural integrity of the nanoparticles, ensuring efficient mRNA expression within the spinal cord. Secondly, the MP-LNP formulation effectively attenuates inflammation and reduces the adverse effects associated with high-dose MP treatment in the acute phase of SCI. Lastly, MP-LNP-C3 demonstrates notable neuroprotective properties and promotes enhanced recovery of motor function in SCI mouse models. Together, these results underscore the potential of this innovative LNP-based therapy as a promising avenue for advancing the treatment of clinical SCI. Graphical Abstract |
| format | Article |
| id | doaj-art-684885a7537f4236b7240fae1b7723c2 |
| institution | Kabale University |
| issn | 1477-3155 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj-art-684885a7537f4236b7240fae1b7723c22025-02-09T12:52:57ZengBMCJournal of Nanobiotechnology1477-31552025-02-0123111710.1186/s12951-025-03153-zMethylprednisolone substituted lipid nanoparticles deliver C3 transferase mRNA for combined treatment of spinal cord injuryHaoru Dong0Zongxing He1Shiyi Cai2Haiqiang Ma3Lili Su4Jianfeng Li5Huiying Yang6Rong Xie7Department of Neurosurgery, National Center for Neurological Disorders, Neurosurgical Institute of Fudan University, Shanghai Clinical Medical Center of Neurosurgery, Shanghai Key Laboratory of Brain Function and Restoration and Neural Regeneration, Huashan Hospital, Fudan UniversitySchool of Life Science and Technology & State Key Laboratory of Advanced Medical Materials and Devices, ShanghaiTech UniversityDepartment of Neurosurgery, National Center for Neurological Disorders, Neurosurgical Institute of Fudan University, Shanghai Clinical Medical Center of Neurosurgery, Shanghai Key Laboratory of Brain Function and Restoration and Neural Regeneration, Huashan Hospital, Fudan UniversityDepartment of Neurosurgery, National Center for Neurological Disorders, Neurosurgical Institute of Fudan University, Shanghai Clinical Medical Center of Neurosurgery, Shanghai Key Laboratory of Brain Function and Restoration and Neural Regeneration, Huashan Hospital, Fudan UniversitySchool of Life Science and Technology & State Key Laboratory of Advanced Medical Materials and Devices, ShanghaiTech UniversitySchool of Life Science and Technology & State Key Laboratory of Advanced Medical Materials and Devices, ShanghaiTech UniversityDepartment of Pharmacy, Huashan Hospital, Fudan UniversityDepartment of Neurosurgery, National Center for Neurological Disorders, Neurosurgical Institute of Fudan University, Shanghai Clinical Medical Center of Neurosurgery, Shanghai Key Laboratory of Brain Function and Restoration and Neural Regeneration, Huashan Hospital, Fudan UniversityAbstract Spinal cord injury (SCI), characterized by the disruption of neural pathways and an increase in inflammatory cell infiltration, leads to profound and lasting neurological deficits, with a high risk of resulting in permanent disability. Currently, the therapeutic landscape for SCI is notably sparse, with limited effective treatment options available. Methylprednisolone (MP), a widely used clinical anti-inflammatory agent for SCI, requires administration in high doses that are associated with significant adverse effects. In this study, we introduce an innovative approach by substituting cholesterol with MP to engineer a novel Lipid Nanoparticle (MP-LNP). This strategy aims to enhance the localization and concentration of MP at the injury site, thereby amplifying its therapeutic efficacy while mitigating systemic side effects. Furthermore, we explore the integration of C3 transferase mRNA into MP-LNPs. C3 transferase, a potent inhibitor of the RhoA pathway, has shown promise in facilitating neurological recovery in animal models of SCI and is currently being evaluated in clinical trials. The novel formulation, MP-LNP-C3, is designed for direct administration to the injury site during decompression surgery, offering a targeted therapeutic modality for SCI. Our findings reveal several significant advantages of this approach: Firstly, the incorporation of C3 transferase mRNA into MP-LNPs does not compromise the structural integrity of the nanoparticles, ensuring efficient mRNA expression within the spinal cord. Secondly, the MP-LNP formulation effectively attenuates inflammation and reduces the adverse effects associated with high-dose MP treatment in the acute phase of SCI. Lastly, MP-LNP-C3 demonstrates notable neuroprotective properties and promotes enhanced recovery of motor function in SCI mouse models. Together, these results underscore the potential of this innovative LNP-based therapy as a promising avenue for advancing the treatment of clinical SCI. Graphical Abstracthttps://doi.org/10.1186/s12951-025-03153-zSpinal cord injuryLNPC3 transferaseMethylprednisoloneAnti-inflammationNeuroprotection |
| spellingShingle | Haoru Dong Zongxing He Shiyi Cai Haiqiang Ma Lili Su Jianfeng Li Huiying Yang Rong Xie Methylprednisolone substituted lipid nanoparticles deliver C3 transferase mRNA for combined treatment of spinal cord injury Journal of Nanobiotechnology Spinal cord injury LNP C3 transferase Methylprednisolone Anti-inflammation Neuroprotection |
| title | Methylprednisolone substituted lipid nanoparticles deliver C3 transferase mRNA for combined treatment of spinal cord injury |
| title_full | Methylprednisolone substituted lipid nanoparticles deliver C3 transferase mRNA for combined treatment of spinal cord injury |
| title_fullStr | Methylprednisolone substituted lipid nanoparticles deliver C3 transferase mRNA for combined treatment of spinal cord injury |
| title_full_unstemmed | Methylprednisolone substituted lipid nanoparticles deliver C3 transferase mRNA for combined treatment of spinal cord injury |
| title_short | Methylprednisolone substituted lipid nanoparticles deliver C3 transferase mRNA for combined treatment of spinal cord injury |
| title_sort | methylprednisolone substituted lipid nanoparticles deliver c3 transferase mrna for combined treatment of spinal cord injury |
| topic | Spinal cord injury LNP C3 transferase Methylprednisolone Anti-inflammation Neuroprotection |
| url | https://doi.org/10.1186/s12951-025-03153-z |
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