Nanotechnology approach for drug addiction therapy: Gene silencing using delivery of gold nanorod-siRNA nanoplex in dopaminergic neurons
Nanotechnology approach for drug addiction therapy: Gene silencing using delivery of gold nanorod-siRNA nanoplex in dopaminergic neurons
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DOI：
10.1073/pnas.0901715106
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发表时间：
2009-04-07
影响因子：
11.1
通讯作者：
Prasad, Paras N.
中科院分区：
文献类型：
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作者：
Bonoiu, Adela C.;Mahajan, Supriya D.;Prasad, Paras N.
药物滥用是一个全球性的健康问题，其中成瘾涉及大脑中多巴胺能信号通路的激活。在这里，我们介绍了一种纳米技术方法，该方法利用金纳米棒-DARPP-32 siRNA复合物（纳米复合物）来靶向大脑中的多巴胺能信号通路。金纳米棒（GNR）的局部纵向等离子体共振峰的位移用于显示它们与siRNA的相互作用。等离子体增强暗场成像用于可视化这些纳米复合物在体外多巴胺能神经元中的摄取。这些细胞中纳米复合物的基因沉默通过属于该途径的关键蛋白质（DARPP-32、ERK和PP-1）的表达减少来证明，没有观察到细胞毒性。此外，这些纳米复合物显示出穿过血脑屏障（BBB）的体外模型。因此，这些纳米复合物似乎适合于适当siRNA的脑特异性递送，用于药物成瘾和其他脑疾病的治疗。
Drug abuse is a worldwide health concern in which addiction involves activation of the dopaminergic signaling pathway in the brain. Here, we introduce a nanotechnology approach that utilizes gold nanorod-DARPP-32 siRNA complexes (nanoplexes) that target this dopaminergic signaling pathway in the brain. The shift in the localized longitudinal plasmon resonance peak of gold nanorods (GNRs) was used to show their interaction with siRNA. Plasmonic enhanced dark field imaging was used to visualize the uptake of these nanoplexes in dopaminergic neurons in vitro. Gene silencing of the nanoplexes in these cells was evidenced by the reduction in the expression of key proteins (DARPP-32, ERK, and PP-1) belonging to this pathway, with no observed cytotoxicity. Moreover, these nanoplexes were shown to transmigrate across an in vitro model of the blood-brain barrier (BBB). Therefore, these nanoplexes appear to be suited for brain-specific delivery of appropriate siRNA for therapy of drug addiction and other brain diseases.