Theranostics 2021; 11(17):8197-8217. doi:10.7150/thno.58947
Early administration of MPC-n(IVIg) selectively accumulates in ischemic areas to protect inflammation-induced brain damage from ischemic stroke
1. Department of Neurosurgery, Tianjin Medical University General Hospital, Laboratory of Neuro-oncology, Tianjin Neurological Institute, Key Laboratory of Post-Neurotrauma Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin 300052, China.
2. Tianjin Key Laboratory of Composite and Functional Materials, School of Materials Science and Engineering, Tianjin University, Tianjin 300072, China.
3. Tianjin Key Laboratory of Cerebral Vascular and Neurodegenerative Diseases, Tianjin Neurosurgical Institute, Tianjin Huanhu Hospital, Tianjin 300350, China. Department of Neurology, Tianjin Huanhu Hospital, Tianjin 300350, China.
These authors contributed equally: Weili Jin, Ye Wu
Jin W, Wu Y, Chen N, Wang Q, Wang Y, Li Y, Li S, Han X, Yang E, Tong F, Wu J, Yuan X, Kang C. Early administration of MPC-n(IVIg) selectively accumulates in ischemic areas to protect inflammation-induced brain damage from ischemic stroke. Theranostics 2021; 11(17):8197-8217. doi:10.7150/thno.58947. Available from https://www.thno.org/v11p8197.htm
Ischemic stroke is an acute and severe neurological disease, which leads to disability and death. Immunomodulatory therapies exert multiple remarkable protective effects during ischemic stroke. However, patients suffering from ischemic stroke do not benefit from immunomodulatory therapies due to the presence of the blood-brain barrier (BBB) and their off-target effects.
Methods: We presented a delivery strategy to optimize immunomodulatory therapies by facilitating BBB penetration and selectively delivering intravenous immunoglobulin (IVIg) to ischemic regions using 2-methacryloyloxyethyl phosphorylcholine (MPC)-nanocapsules, MPC-n(IVIg), synthesized using MPC monomers and ethylene glycol dimethyl acrylate (EGDMA) crosslinker via in situ polymerization. In vitro and in vivo experiments verify the effect and safety of MPC-n(IVIg).
Results: MPC-n(IVIg) efficiently crosses the BBB and IVIg selectively accumulates in ischemic areas in a high-affinity choline transporter 1 (ChT1)-overexpression dependent manner via endothelial cells in ischemic areas. Moreover, earlier administration of MPC-n(IVIg) more efficiently deliver IVIg to ischemic areas. Furthermore, the early administration of low-dosage MPC-n(IVIg) decreases neurological deficits and mortality by suppressing stroke-induced inflammation in the middle cerebral artery occlusion model.
Conclusion: Our findings indicate a promising strategy to efficiently deliver the therapeutics to the ischemic target brain tissue and lower the effective dose of therapeutic drugs for treating ischemic strokes.
Keywords: blood-brain barrier, selective accumulation, intravenous immunoglobulin, immunomodulatory therapy, ischemic stroke