Bioactive Self‐Assembled Nanoregulator Enhances Hematoma Resolution and Inhibits Neuroinflammation in the Treatment of Intracerebral Hemorrhage
Abstract Hematoma and secondary neuroinflammation continue to pose a significant challenge in the clinical treatment of intracerebral hemorrhage (ICH). This study describes a nanoregulator formed through the self‐assembly of Mg2+ and signal regulatory protein α (SIRPα) DNAzyme (SDz), aimed at enhanc...
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| Format: | Article |
| Language: | English |
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Wiley
2025-01-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202408647 |
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| author | Wenyan Yu Chengyuan Che Yi Yang Yuzhen Zhao Junjie Liu Aibing Chen Jinjin Shi |
| author_facet | Wenyan Yu Chengyuan Che Yi Yang Yuzhen Zhao Junjie Liu Aibing Chen Jinjin Shi |
| author_sort | Wenyan Yu |
| collection | DOAJ |
| description | Abstract Hematoma and secondary neuroinflammation continue to pose a significant challenge in the clinical treatment of intracerebral hemorrhage (ICH). This study describes a nanoregulator formed through the self‐assembly of Mg2+ and signal regulatory protein α (SIRPα) DNAzyme (SDz), aimed at enhancing hematoma resolution and inhibiting neuroinflammation in the treatment of ICH. The structure of SDz collapses in response to the acidic endo/lysosomal microenvironment of microglia, releasing Mg2+ and the SIRPα DNAzyme. The Mg2+ then acts as a cofactor to activate the SIRPα DNAzyme. By blocking the CD47‐SIRPα signaling pathway, microglia can rapidly and effectively phagocytose red blood cells (RBCs), thereby promoting the clearance of the hematoma. Simultaneously, Mg2+ reset the microglia to the M2 phenotype by inhibiting the MYD88/MAPK/NF‐κB signaling pathway, thereby modulating the inflammatory microenvironment of ICH. This co‐delivery and synergistic strategy resulted in a significant reduction in hematoma size, decreasing from 11.90 to 5.84 mm3, and promoted recovery from ICH with minimal systemic side effects. This simple yet highly effective nanoplatform, which involves complex synergistic mechanisms, proves to be effective for ICH therapy and holds great promise for introducing novel perspectives into clinical and translational approaches for ICH. |
| format | Article |
| id | doaj-art-b829cd3ff54748a38500b76bcc87aacb |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-b829cd3ff54748a38500b76bcc87aacb2025-01-09T11:44:45ZengWileyAdvanced Science2198-38442025-01-01121n/an/a10.1002/advs.202408647Bioactive Self‐Assembled Nanoregulator Enhances Hematoma Resolution and Inhibits Neuroinflammation in the Treatment of Intracerebral HemorrhageWenyan Yu0Chengyuan Che1Yi Yang2Yuzhen Zhao3Junjie Liu4Aibing Chen5Jinjin Shi6School of Pharmaceutical Sciences Zhengzhou University Zhengzhou 450001 ChinaCollege of Chemical and Pharmaceutical Engineering Hebei University of Science and Technology Shijiazhuang 050018 ChinaSchool of Pharmaceutical Sciences Zhengzhou University Zhengzhou 450001 ChinaSchool of Pharmaceutical Sciences Zhengzhou University Zhengzhou 450001 ChinaSchool of Pharmaceutical Sciences Zhengzhou University Zhengzhou 450001 ChinaCollege of Chemical and Pharmaceutical Engineering Hebei University of Science and Technology Shijiazhuang 050018 ChinaSchool of Pharmaceutical Sciences Zhengzhou University Zhengzhou 450001 ChinaAbstract Hematoma and secondary neuroinflammation continue to pose a significant challenge in the clinical treatment of intracerebral hemorrhage (ICH). This study describes a nanoregulator formed through the self‐assembly of Mg2+ and signal regulatory protein α (SIRPα) DNAzyme (SDz), aimed at enhancing hematoma resolution and inhibiting neuroinflammation in the treatment of ICH. The structure of SDz collapses in response to the acidic endo/lysosomal microenvironment of microglia, releasing Mg2+ and the SIRPα DNAzyme. The Mg2+ then acts as a cofactor to activate the SIRPα DNAzyme. By blocking the CD47‐SIRPα signaling pathway, microglia can rapidly and effectively phagocytose red blood cells (RBCs), thereby promoting the clearance of the hematoma. Simultaneously, Mg2+ reset the microglia to the M2 phenotype by inhibiting the MYD88/MAPK/NF‐κB signaling pathway, thereby modulating the inflammatory microenvironment of ICH. This co‐delivery and synergistic strategy resulted in a significant reduction in hematoma size, decreasing from 11.90 to 5.84 mm3, and promoted recovery from ICH with minimal systemic side effects. This simple yet highly effective nanoplatform, which involves complex synergistic mechanisms, proves to be effective for ICH therapy and holds great promise for introducing novel perspectives into clinical and translational approaches for ICH.https://doi.org/10.1002/advs.202408647drug deliveryhematoma clearanceintracerebral hemorrhage therapymicroglia polarizationnanotechnology |
| spellingShingle | Wenyan Yu Chengyuan Che Yi Yang Yuzhen Zhao Junjie Liu Aibing Chen Jinjin Shi Bioactive Self‐Assembled Nanoregulator Enhances Hematoma Resolution and Inhibits Neuroinflammation in the Treatment of Intracerebral Hemorrhage Advanced Science drug delivery hematoma clearance intracerebral hemorrhage therapy microglia polarization nanotechnology |
| title | Bioactive Self‐Assembled Nanoregulator Enhances Hematoma Resolution and Inhibits Neuroinflammation in the Treatment of Intracerebral Hemorrhage |
| title_full | Bioactive Self‐Assembled Nanoregulator Enhances Hematoma Resolution and Inhibits Neuroinflammation in the Treatment of Intracerebral Hemorrhage |
| title_fullStr | Bioactive Self‐Assembled Nanoregulator Enhances Hematoma Resolution and Inhibits Neuroinflammation in the Treatment of Intracerebral Hemorrhage |
| title_full_unstemmed | Bioactive Self‐Assembled Nanoregulator Enhances Hematoma Resolution and Inhibits Neuroinflammation in the Treatment of Intracerebral Hemorrhage |
| title_short | Bioactive Self‐Assembled Nanoregulator Enhances Hematoma Resolution and Inhibits Neuroinflammation in the Treatment of Intracerebral Hemorrhage |
| title_sort | bioactive self assembled nanoregulator enhances hematoma resolution and inhibits neuroinflammation in the treatment of intracerebral hemorrhage |
| topic | drug delivery hematoma clearance intracerebral hemorrhage therapy microglia polarization nanotechnology |
| url | https://doi.org/10.1002/advs.202408647 |
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