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跨越血脑屏障!金纳米粒RNA载药系统治疗脑瘤显疗效

来源:生物谷 2015-04-15 10:06

2015年4月14日讯 /生物谷BIOON/ --血脑屏障是指脑毛细血管壁与神经胶质细胞形成的血浆与脑细胞之间的屏障和由脉络丛形成的血浆和脑脊液之间的屏障,这些屏障能够阻止某些物质(多半是有害的)由血液进入脑组织。这种有选择性的通透现象使人们设想可能有限制溶质透过的某种结构存在,这种结构可使脑组织少受甚至不受循环血液中有害物质的损害,从而保持脑组织内环境的基本稳定,对维持中枢神经系统正常生理状态具有重要的生物学意义。

由于脑血管障壁几乎不让所有的物质通过,除了氧气、二氧化碳和血糖,大部分的药和蛋白质由于分子结构过大,一般无法通过。因此血脑屏障也成为了生物医药研究中挥之不去的噩梦。可以说相当一部分脑部疾病药物研究最终折戟的重要原因就是无法克服血脑屏障这个问题。

而近些年来载药系统的发展为克服这一问题提供了很好的借鉴。最近,来自美国西北大学的研究人员利用一种金纳米颗粒载药系统成功将RNA分子跨过血脑屏障输送至脑部用于治疗多形性成胶质细胞瘤。这种名为miR-182的RNA分子能够抑制与胶质细胞瘤相关基因的表达并达到治疗肿瘤的效果。另一方面,考虑到RNA本身是一种较难输送的物质,研究人员获得的这一结果也相当令人瞩目。同时,在这一过程中,这种金纳米颗粒-RNA载药系统避免了跨越血脑屏障时可能会产生的毒副作用。

研究人员在研究中采用的纳米结构被称为球形核酸分子结构(SNA),这一结构在当今RNA输送研究中有着广泛的应用。目前研究人员已经将这一结果发表在了 Genes and Development杂志上。(生物谷Bioon.com)

详细英文报道:

Researchers at Northwestern University have put together a nanostructure capable of shuttling a new RNA molecule across the blood-brain barrier to reach tumor cells in mice with glioblastoma multiforme, a particularly aggressive form of brain cancer.

The newly discovered miR-182 RNA molecule has shown potential in the suppression of genes in the brain that cause cancer. But getting past the blood-brain barrier has always been a challenge, so delivery of the molecule is especially important for the RNA's success. In fact, the delivery challenges are two-fold, because RNA itself is a troubling prospect because of its resistance to transport in vivo.

But using spherical nucleic acids, the scientists were able to safely deliver miR-182 to the brain to target multiple oncogenes in one go, killing cancer cells and reducing its growth potential.

"We demonstrate a more specific, more personalized approach to therapy," lead researcher Alexander Stegh said in a statement. "SNAs are a very promising platform to silence the particular genes that drive or contribute to cancer progression in individual patients."

The delivery particles demonstrate a disguise property that allows them to pass through the challenging blood-brain barrier without toxicity or immune response.

"We designed a novel delivery method for miR-182 using (spherical nucleic acids)," Stegh said. "Small gold nanoparticles are conjugated with miR-182 sequences. They cross the blood-brain/blood-tumor barrier, and accumulate within brain tumor sites, where they target oncogenes, regulate cell growth and differentiation, reduce tumor burden and prolong survival in our mouse models."

 

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