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Abstract：
Aim: Alterations of microglia, the brain-resident macrophages, are associated with numerous brain pathologies. Genetic manipulation of microglia in diseases using small interfering RNA (siRNA) is hampered by the lack of safe and efficient siRNA delivery methods. We assessed the amphiphilic dendrimer (AD) for functional siRNA delivery and gene knockdown in primary microglia. Materials & methods: We characterized the ability of AD to form nanoparticles with siRNA, and studied their size, surface potential, cell uptake and gene silencing in rodent microglia. Results: AD effectively delivered siRNA to primary microglia and decreased target gene and protein expression, leading to transcriptomic changes without affecting basal microglial functions. Conclusion: The dendrimer AD promises to be an innocuous carrier for siRNA delivery into microglia.
摘要：
目的：小胶质细胞的改变，大脑驻留的巨噬细胞，与许多脑部疾病有关。使用小干扰RNA(siRNA)的疾病中的小胶质细胞的遗传操作由于缺乏安全和有效的siRNA递送方法而受到阻碍。我们评估了两亲性树状聚合物（AD）在原发性小胶质细胞中的功能性siRNA递送和基因敲低。材料与方法：我们表征了AD与siRNA形成纳米颗粒的能力，研究了它们的大小，表面电势,啮齿动物小胶质细胞的细胞摄取和基因沉默。结果:AD有效地将siRNA传递给原代小胶质细胞,降低靶基因和蛋白的表达,导致转录组变化而不影响基础小胶质细胞功能。结论：树枝状聚合物AD有望成为将siRNA递送到小胶质细胞中的无害载体。
