Development and application of a dual-purpose nanoparticle platform for delivery and imaging of siRNA in tumors.

Development and application of a dual-purpose nanoparticle platform for delivery and imaging of siRNA in tumors.
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开发和应用双用途纳米颗粒平台,用于肿瘤中 siRNA 的递送和成像。

DOI:
10.1007/978-1-60327-295-7_1
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发表时间:
2009
期刊:
Methods in molecular biology (Clifton, N.J.)
影响因子:
--
通讯作者:
Moore,Anna
Moore,Anna
中科院分区:
--
文献类型:
--
作者:
Medarova,Zdravka;Kumar,Mohanraja;Ng,Shu-wing;Moore,Anna

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The vision of using a single therapeutic agent with sufficient generality to allow application to a wide variety of diseases, yet specific enough to permit intervention at single molecular stages of the pathology, is rapidly becoming a reality through the emergence of RNA interference. RNA interference can be used to inhibit the expression of virtually any gene and, at the same time, has single-nucleotide specificity. Major challenges in applying RNA interference in vivo are adequate delivery of the siRNA molecule to the tissue of interest and methods of monitoring this delivery in a noninvasive manner. With this in mind, we have developed an approach not only to deliver siRNA to tumors, but also to track the success of the delivery by noninvasive imaging. To accomplish this, we designed a dual-function probe, MN-NIRF-siRNA, which consists of magnetic nanoparticles (MN) for magnetic resonance imaging (MRI), labeled with Cy5.5 dye for near-infrared in vivo optical imaging (NIRF), conjugated to myristoylated polyarginine peptides (MPAPs) for translocation of the complex into the cytosol, and carrying siRNA targeting tumor-specific genes. Administration of MN-NIRF-siRNA to tumor-bearing mice allowed us to monitor the delivery of the agent to tumors by MRI and NIRF imaging and resulted in efficient silencing of the target genes. This approach can significantly advance the therapeutic potential of RNA interference by providing a way not only to effectively shuttle siRNA to target sites but also to noninvasively assess the bioavailability of the siRNA molecule.
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