NET formation-mediated in situ protein delivery to the inflamed central nervous system
Abstract Delivering protein drugs to the central nervous system (CNS) is challenging due to the blood-brain and blood-spinal cord barrier. Here we show that neutrophils, which naturally migrate through these barriers to inflamed CNS sites and release neutrophil extracellular traps (NETs), can be lev...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2024-12-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-54817-7 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832585556499890176 |
|---|---|
| author | Yina Wu Jinwon Park Quoc-Viet Le Junho Byun Jaehyun Choi Enzhen Xu Jaiwoo Lee Yu-Kyoung Oh |
| author_facet | Yina Wu Jinwon Park Quoc-Viet Le Junho Byun Jaehyun Choi Enzhen Xu Jaiwoo Lee Yu-Kyoung Oh |
| author_sort | Yina Wu |
| collection | DOAJ |
| description | Abstract Delivering protein drugs to the central nervous system (CNS) is challenging due to the blood-brain and blood-spinal cord barrier. Here we show that neutrophils, which naturally migrate through these barriers to inflamed CNS sites and release neutrophil extracellular traps (NETs), can be leveraged for therapeutic delivery. Tannic acid nanoparticles tethered with anti-Ly6G antibody and interferon-β (aLy6G-IFNβ@TLP) are constructed for targeted neutrophil delivery. These nanoparticles protect interferon-β from reactive oxygen species and preferentially accumulate in neutrophils over other immune cells. Upon encountering inflammation, neutrophils release the nanoparticles during NET formation. In the female mouse model of experimental autoimmune encephalomyelitis, intravenous administration of aLy6G-IFNβ@TLP reduce disease progression and restore motor function. Although this study focuses on IFNβ and autoimmune encephalomyelitis, the concept of hitchhiking neutrophils for CNS delivery and employing NET formation for inflamed site-specific nanoparticle release can be further applied for delivery of other protein drugs in the treatment of neurodegenerative diseases. |
| format | Article |
| id | doaj-art-374f8a05bee34df1a383708b368ee2de |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-374f8a05bee34df1a383708b368ee2de2025-01-26T12:40:09ZengNature PortfolioNature Communications2041-17232024-12-0115111610.1038/s41467-024-54817-7NET formation-mediated in situ protein delivery to the inflamed central nervous systemYina Wu0Jinwon Park1Quoc-Viet Le2Junho Byun3Jaehyun Choi4Enzhen Xu5Jaiwoo Lee6Yu-Kyoung Oh7College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National UniversityCollege of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National UniversityFaculty of Pharmacy, Ton Duc Thang UniversityCollege of Pharmacy, Sookmyung Women’s UniversityCollege of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National UniversityCollege of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National UniversityCollege of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National UniversityCollege of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National UniversityAbstract Delivering protein drugs to the central nervous system (CNS) is challenging due to the blood-brain and blood-spinal cord barrier. Here we show that neutrophils, which naturally migrate through these barriers to inflamed CNS sites and release neutrophil extracellular traps (NETs), can be leveraged for therapeutic delivery. Tannic acid nanoparticles tethered with anti-Ly6G antibody and interferon-β (aLy6G-IFNβ@TLP) are constructed for targeted neutrophil delivery. These nanoparticles protect interferon-β from reactive oxygen species and preferentially accumulate in neutrophils over other immune cells. Upon encountering inflammation, neutrophils release the nanoparticles during NET formation. In the female mouse model of experimental autoimmune encephalomyelitis, intravenous administration of aLy6G-IFNβ@TLP reduce disease progression and restore motor function. Although this study focuses on IFNβ and autoimmune encephalomyelitis, the concept of hitchhiking neutrophils for CNS delivery and employing NET formation for inflamed site-specific nanoparticle release can be further applied for delivery of other protein drugs in the treatment of neurodegenerative diseases.https://doi.org/10.1038/s41467-024-54817-7 |
| spellingShingle | Yina Wu Jinwon Park Quoc-Viet Le Junho Byun Jaehyun Choi Enzhen Xu Jaiwoo Lee Yu-Kyoung Oh NET formation-mediated in situ protein delivery to the inflamed central nervous system Nature Communications |
| title | NET formation-mediated in situ protein delivery to the inflamed central nervous system |
| title_full | NET formation-mediated in situ protein delivery to the inflamed central nervous system |
| title_fullStr | NET formation-mediated in situ protein delivery to the inflamed central nervous system |
| title_full_unstemmed | NET formation-mediated in situ protein delivery to the inflamed central nervous system |
| title_short | NET formation-mediated in situ protein delivery to the inflamed central nervous system |
| title_sort | net formation mediated in situ protein delivery to the inflamed central nervous system |
| url | https://doi.org/10.1038/s41467-024-54817-7 |
| work_keys_str_mv | AT yinawu netformationmediatedinsituproteindeliverytotheinflamedcentralnervoussystem AT jinwonpark netformationmediatedinsituproteindeliverytotheinflamedcentralnervoussystem AT quocvietle netformationmediatedinsituproteindeliverytotheinflamedcentralnervoussystem AT junhobyun netformationmediatedinsituproteindeliverytotheinflamedcentralnervoussystem AT jaehyunchoi netformationmediatedinsituproteindeliverytotheinflamedcentralnervoussystem AT enzhenxu netformationmediatedinsituproteindeliverytotheinflamedcentralnervoussystem AT jaiwoolee netformationmediatedinsituproteindeliverytotheinflamedcentralnervoussystem AT yukyoungoh netformationmediatedinsituproteindeliverytotheinflamedcentralnervoussystem |