Gold nanorod--siRNA induces efficient in vivo gene silencing in the rat hippocampus.

Gold nanorod--siRNA induces efficient in vivo gene silencing in the rat hippocampus.
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DOI:
10.2217/nnm.11.20
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发表时间:
2011-06
期刊:
Nanomedicine (London, England)
影响因子:
--
通讯作者:
Ignatowski TA
Ignatowski TA
中科院分区:
其他
文献类型:
--
作者:
Bonoiu AC;Bergey EJ;Ding H;Hu R;Kumar R;Yong KT;Prasad PN;Mahajan S;Picchione KE;Bhattacharjee A;Ignatowski TA

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金纳米棒(GNRs),细胞成像纳米探针,已被用于药物递送治疗的免疫特权区域在大脑中。我们证明,带负电荷的RNA和带正电荷的GNRs之间的静电结合形成的纳米复合物,沉默的目标管家基因的表达,甘油醛3-磷酸脱氢酶(GAPDH)在大鼠大脑的CA 1海马区,而不显示细胞毒性。使用siRNAC γ 3GAPDH的荧光成像和使用来自GNR的等离子体增强散射的暗场成像来监测纳米复合物在靶向海马区域中存在的不同神经元细胞类型内的分布。我们的结果显示了荧光基因沉默物的稳健的纳米复合物摄取和缓慢释放,对GAPDH基因表达的抑制具有显著影响(70%基因沉默,注射后>10天)。在大脑的目标区域使用纳米复合物观察到的基因敲低开启了神经系统疾病药物治疗的新时代。
Gold nanorods (GNRs), cellular imaging nanoprobes, have been used for drug delivery therapy to immunologically privileged regions in the brain. We demonstrate that nanoplexes formed by electrostatic binding between negatively charged RNA and positively charged GNRs, silence the expression of the target housekeeping gene, glyceraldehyde 3-phosphate dehydrogenase (GAPDH) within the CA1 hippocampal region of the rat brain, without showing cytotoxicity. Fluorescence imaging with siRNACy3GAPDH and dark field imaging using plasmonic enhanced scattering from GNRs were used to monitor the distribution of the nanoplexes within different neuronal cell types present in the targeted hippocampal region. Our results show robust nanoplex uptake and slow release of the fluorescent gene silencer with significant impact on suppression of GAPDH gene expression (70% gene silencing, >10 days post-injection). The observed gene knockdown using nanoplexes in targeted regions of the brain opens a new era of drug treatment for neurological disorders.