NEP1-40-modified human serum albumin nanoparticles enhance the therapeutic effect of methylprednisolone against spinal cord injury
Abstract Background Frequent injection of high-dose methylprednisolone (MP) is used to treat spinal cord injury (SCI), but free MP is associated with various side effects and its water solubility is low, limiting potential dosing regimes and administration routes. Albumin-based nanoparticles, which...
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| Format: | Article |
| Language: | English |
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BMC
2019-01-01
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| Series: | Journal of Nanobiotechnology |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12951-019-0449-3 |
| _version_ | 1798026007168417792 |
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| author | Yan Lin Chunhong Li Jian Li Ruolan Deng Juan Huang Qinglian Zhang Jiayao Lyu Na Hao Zhirong Zhong |
| author_facet | Yan Lin Chunhong Li Jian Li Ruolan Deng Juan Huang Qinglian Zhang Jiayao Lyu Na Hao Zhirong Zhong |
| author_sort | Yan Lin |
| collection | DOAJ |
| description | Abstract Background Frequent injection of high-dose methylprednisolone (MP) is used to treat spinal cord injury (SCI), but free MP is associated with various side effects and its water solubility is low, limiting potential dosing regimes and administration routes. Albumin-based nanoparticles, which can encapsulate therapeutic drugs and release cargo in a controlled pattern, show high biocompatibility and low toxicity. The Nogo protein, expressed on the surface of oligodendrocytes, can inhibit axonal growth by binding with the axonal Nogo receptor (NgR). Peptide NEP1-40, an NgR antagonist, can bind specifically to Nogo, significantly improving functional recovery and axon growth in the corticospinal tract. Therefore, we hypothesized that delivering MP within nanoparticles decorated with NEP1-40 could avoid the disadvantages of free MP and enhance its therapeutic efficacy against SCI. Results We used human serum albumin to prepare MP-loaded NPs (MP-NPs), to whose surface we conjugated NEP1-40 to form NEP1-40-MP-NPs. Transmission electron microscopy indicated successful formation of nanoparticles. NEP1-40-MP-NPs were taken up significantly better than MP-NPs by the Nogo-positive cell line RSC-96 and were associated with significantly higher Basso–Beattie–Bresnahan locomotor scores in rats recovering from SCI. Micro-computed tomography assay showed that NEP1-40-MP-NPs mitigated SCI-associated loss of bone mineral density and accelerated spinal cord repair. Conclusions NEP1-40-MP-NPs can enhance the therapeutic effects of MP against SCI. This novel platform may also be useful for delivering other types of drugs. |
| first_indexed | 2024-04-11T18:29:20Z |
| format | Article |
| id | doaj.art-004c7dbb3d7d4e0d9a76150725faa405 |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-04-11T18:29:20Z |
| publishDate | 2019-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-004c7dbb3d7d4e0d9a76150725faa4052022-12-22T04:09:31ZengBMCJournal of Nanobiotechnology1477-31552019-01-0117111510.1186/s12951-019-0449-3NEP1-40-modified human serum albumin nanoparticles enhance the therapeutic effect of methylprednisolone against spinal cord injuryYan Lin0Chunhong Li1Jian Li2Ruolan Deng3Juan Huang4Qinglian Zhang5Jiayao Lyu6Na Hao7Zhirong Zhong8Department of Pharmaceutical Sciences, School of Pharmacy, Southwest Medical UniversityDepartment of Pharmaceutical Sciences, School of Pharmacy, Southwest Medical UniversityDepartment of Pharmaceutical Sciences, School of Pharmacy, Southwest Medical UniversityDepartment of Pharmaceutical Sciences, School of Pharmacy, Southwest Medical UniversityLuzhou TCM HospitalLuzhou TCM HospitalDepartment of Pharmaceutical Sciences, School of Pharmacy, Southwest Medical UniversityDepartment of Pharmaceutical Sciences, School of Pharmacy, Southwest Medical UniversityDepartment of Pharmaceutical Sciences, School of Pharmacy, Southwest Medical UniversityAbstract Background Frequent injection of high-dose methylprednisolone (MP) is used to treat spinal cord injury (SCI), but free MP is associated with various side effects and its water solubility is low, limiting potential dosing regimes and administration routes. Albumin-based nanoparticles, which can encapsulate therapeutic drugs and release cargo in a controlled pattern, show high biocompatibility and low toxicity. The Nogo protein, expressed on the surface of oligodendrocytes, can inhibit axonal growth by binding with the axonal Nogo receptor (NgR). Peptide NEP1-40, an NgR antagonist, can bind specifically to Nogo, significantly improving functional recovery and axon growth in the corticospinal tract. Therefore, we hypothesized that delivering MP within nanoparticles decorated with NEP1-40 could avoid the disadvantages of free MP and enhance its therapeutic efficacy against SCI. Results We used human serum albumin to prepare MP-loaded NPs (MP-NPs), to whose surface we conjugated NEP1-40 to form NEP1-40-MP-NPs. Transmission electron microscopy indicated successful formation of nanoparticles. NEP1-40-MP-NPs were taken up significantly better than MP-NPs by the Nogo-positive cell line RSC-96 and were associated with significantly higher Basso–Beattie–Bresnahan locomotor scores in rats recovering from SCI. Micro-computed tomography assay showed that NEP1-40-MP-NPs mitigated SCI-associated loss of bone mineral density and accelerated spinal cord repair. Conclusions NEP1-40-MP-NPs can enhance the therapeutic effects of MP against SCI. This novel platform may also be useful for delivering other types of drugs.http://link.springer.com/article/10.1186/s12951-019-0449-3NEP1-40Human serum albumin nanoparticlesMethylprednisoloneSpinal cord injury |
| spellingShingle | Yan Lin Chunhong Li Jian Li Ruolan Deng Juan Huang Qinglian Zhang Jiayao Lyu Na Hao Zhirong Zhong NEP1-40-modified human serum albumin nanoparticles enhance the therapeutic effect of methylprednisolone against spinal cord injury Journal of Nanobiotechnology NEP1-40 Human serum albumin nanoparticles Methylprednisolone Spinal cord injury |
| title | NEP1-40-modified human serum albumin nanoparticles enhance the therapeutic effect of methylprednisolone against spinal cord injury |
| title_full | NEP1-40-modified human serum albumin nanoparticles enhance the therapeutic effect of methylprednisolone against spinal cord injury |
| title_fullStr | NEP1-40-modified human serum albumin nanoparticles enhance the therapeutic effect of methylprednisolone against spinal cord injury |
| title_full_unstemmed | NEP1-40-modified human serum albumin nanoparticles enhance the therapeutic effect of methylprednisolone against spinal cord injury |
| title_short | NEP1-40-modified human serum albumin nanoparticles enhance the therapeutic effect of methylprednisolone against spinal cord injury |
| title_sort | nep1 40 modified human serum albumin nanoparticles enhance the therapeutic effect of methylprednisolone against spinal cord injury |
| topic | NEP1-40 Human serum albumin nanoparticles Methylprednisolone Spinal cord injury |
| url | http://link.springer.com/article/10.1186/s12951-019-0449-3 |
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