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Gene Silencing of Human Neuronal Cells for Drug Addiction Therapy using Anisotropic Nanocrystals

机译:人类神经元细胞的基因沉默,使用各向异性纳米晶体进行药物成瘾治疗

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Theranostic platform integrating diagnostic imaging and therapeutic function into a single system has become a new direction of nanoparticle research. In the process of treatment, therapeutic efficacy is monitored. The use of theranostic nanoparticle can add an additional "layer" to keep track on the therapeutic agent such as the pharmacokinetics and biodistribution. In this report, we have developed quantum rod (QR) based formulations for the delivery of small interfering RNAs (siRNAs) to human neuronal cells. PEGlyated QRs with different surface functional groups (amine and maleimide) were designed for selectively down-regulating the dopaminergic signaling pathway which is associated with the drug abuse behavior. We have demonstrated that the DARPP-32 siRNAs were successfully delivered to dopaminergic neuronal (DAN) cells which led to drastic knockdown of specific gene expression by both the electrostatic and covalent bond conjugation regimes. The PEGlyated surface offered high biocompatibilities and negligible cytotoxicities to the QR formulations that may facilitate the in vivo applications of these nanoparticles.
机译:将诊断成像和治疗功能整合到一个系统中的治疗台已经成为纳米颗粒研究的新方向。在治疗过程中,要监测治疗效果。治疗性纳米颗粒的使用可以添加额外的“层”以跟踪治疗剂,例如药代动力学和生物分布。在本报告中,我们开发了基于量子棒(QR)的配方,用于将小干扰RNA(siRNA)传递至人神经元细胞。具有不同表面官能团(胺和马来酰亚胺)的聚乙二醇化QRs被设计用于选择性下调与药物滥用行为相关的多巴胺能信号通路。我们已经证明,DARPP-32 siRNA已成功传递到多巴胺能神经元(DAN)细胞,通过静电和共价键偶联方案导致特异性基因表达的急剧降低。聚乙二醇化表面对QR制剂具有很高的生物相容性,且细胞毒性可忽略不计,这可能有助于这些纳米粒子的体内应用。

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