Nanomedicine:巨噬细胞为中枢神经系统输送治疗性蛋白提供开关

2015-01-04 MedSci MedSci原创

活化的靶向的输送纳米配制的氧化还原酶、过氧化氢酶,在帕金森病动物模型中巨噬细胞的氧化应激变弱,却增加了多巴胺能神经元的存活。优化的药物配方在活细胞中成功的输送是至关重要的。我们早些时候证明将过氧化氢酶融入带有一种合成聚电解质嵌段共聚物的聚离子复合胶束(纳米酶)中,保护酶在巨噬细胞中降解,改善治疗的结果。我们现在报告制造的具有优越结构和疗效指数的纳米酶。 合成、表征和最佳细胞的纳米配方的治疗效果得

活化的靶向的输送纳米配制的氧化还原酶、过氧化氢酶,在帕金森病动物模型中巨噬细胞的氧化应激变弱,却增加了多巴胺能神经元的存活。优化的药物配方在活细胞中成功的输送是至关重要的。我们早些时候证明将过氧化氢酶融入带有一种合成聚电解质嵌段共聚物的聚离子复合胶束(纳米酶)中,保护酶在巨噬细胞中降解,改善治疗的结果。我们现在报告制造的具有优越结构和疗效指数的纳米酶。

合成、表征和最佳细胞的纳米配方的治疗效果得到评估。

配方设计药物载体通常工作来避免在单核细胞和巨噬细胞中的截留,专注于伴有聚乙二醇冠状物的小型纳米颗粒。相比之下,巨噬细胞输送的最佳的纳米酶在这项研究中所报告的,有一个相对较大的大小尺寸(约200 nm),这将提高负载量,从巨噬细胞中释放。此外, 伴有多余的非生物降解的链接器的交联纳米酶确保其细胞毒性低, 在细胞的载体中高效的过氧化氢酶保护。最后,任一激活的巨噬细胞表型(M2)用于这些研究并没有进一步促进脑部炎症, 在体内的神经再生和修复上导致一个微妙但显著的影响。

优化交联纳米酶加载到巨噬细胞,在老鼠模型上减少了神经炎症反应,增加了神经元的存活。重要的是,细胞介导输送的纳米配方设计方案不同于常见的注射制剂的要求。

原始出处

Natalia L Klyachko, Matthew J Haney, Yuling Zhao, Devika S Manickam, Vivek Mahajan, Poornima Suresh, Shawn D Hingtgen, R Lee Mosley, Howard E Gendelman, Alexander V Kabanov, Elena V Batrakova. Macrophages Offer a Paradigm Switch for CNS Delivery of Therapeutic Proteins. Nanomedicine. 2014;9(9):1403-1422

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    2015-12-02 jeanqiuqiu
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    2015-04-28 kalseyzl
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