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使用各向异性纳米晶体对人类神经元细胞进行基因沉默以用于药物成瘾治疗

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

作者信息

Law Wing-Cheung, Mahajan Supriya D, Kopwitthaya Atcha, Reynolds Jessica L, Liu Maixian, Liu Xin, Chen Guanying, Erogbogbo Folarin, Vathy Lisa, Aalinkeel Ravikumar, Schwartz Stanley A, Yong Ken-Tye, Prasad Paras N

机构信息

1. Institute for Lasers, Photonics and Biophotonics, University at Buffalo, State University of New York, Buffalo, NY 14260-4200, USA.

出版信息

Theranostics. 2012;2(7):695-704. doi: 10.7150/thno.3459. Epub 2012 Jul 27.

DOI:10.7150/thno.3459
PMID:22896771
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3418925/
Abstract

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.

摘要

将诊断成像和治疗功能集成到单一系统中的诊疗平台已成为纳米颗粒研究的新方向。在治疗过程中,会监测治疗效果。使用诊疗纳米颗粒可以增加一个额外的“层面”来追踪治疗剂,比如其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)的制剂,用于将小干扰RNA(siRNA)递送至人神经元细胞。设计了具有不同表面官能团(胺和马来酰亚胺)的聚乙二醇化量子棒,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成功递送至多巴胺能神经元(DAN)细胞,通过静电和共价键结合机制导致特定基因表达的大幅下调。聚乙二醇化表面为量子棒制剂提供了高生物相容性和可忽略不计的细胞毒性,这可能有助于这些纳米颗粒的体内应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdce/3418925/5ecde5fc92f7/thnov02p0695g06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdce/3418925/9291adfe2ab4/thnov02p0695g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdce/3418925/a42138bac413/thnov02p0695g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdce/3418925/880c0a64e3f6/thnov02p0695g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdce/3418925/4fccc658561a/thnov02p0695g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdce/3418925/4fd8b4d8ac55/thnov02p0695g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdce/3418925/5ecde5fc92f7/thnov02p0695g06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdce/3418925/9291adfe2ab4/thnov02p0695g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdce/3418925/a42138bac413/thnov02p0695g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdce/3418925/880c0a64e3f6/thnov02p0695g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdce/3418925/4fccc658561a/thnov02p0695g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdce/3418925/4fd8b4d8ac55/thnov02p0695g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdce/3418925/5ecde5fc92f7/thnov02p0695g06.jpg

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