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./nMethods: 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)./nResults: 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./nConclusion: 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.

中文翻译：

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MPC-n（IVIg）的早期给药选择性地在缺血区域积累，以保护炎症引起的缺血性中风脑损伤

缺血性中风是一种急性和严重的神经系统疾病，会导致残疾和死亡。免疫调节疗法在缺血性中风期间发挥多种显着的保护作用。然而，由于血脑屏障 (BBB) 的存在及其脱靶效应，缺血性中风患者无法从免疫调节治疗中受益。/n方法：我们提出了一种通过促进 BBB 渗透来优化免疫调节治疗的递送策略使用 MPC 单体和乙二醇二甲基丙烯酸酯 (EGDMA) 交联剂通过原位聚合合成的 2-甲基丙烯酰氧乙基磷酸胆碱 (MPC)-纳米胶囊 MPC-n(IVIg) 选择性地将静脉内免疫球蛋白 (IVIg) 递送至缺血区域。体外和体内实验验证了 MPC-n(IVIg) 的效果和安全性。/n结果： MPC-n(IVIg) 有效地穿过 BBB，IVIg 在高亲和力胆碱转运蛋白 1 (ChT1) 过表达的缺血区域选择性积累通过缺血区域内皮细胞的依赖方式。此外，早期使用 MPC-n(IVIg) 可以更有效地将 IVIg 输送到缺血区域。此外，低剂量 MPC-n (IVIg) 的早期给药通过抑制大脑中动脉闭塞模型中中风引起的炎症来降低神经功能缺损和死亡率。/n结论： 我们的研究结果表明了一种有前景的策略，可以有效地将治疗药物输送到缺血性靶脑组织，并降低治疗缺血性中风的治疗药物的有效剂量。