Development and Application of a Dual-Purpose Nanoparticle Platform for Delivery and Imaging of siRNA in Tumors
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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.
Key wordsRNA interference magnetic resonance imaging near-infrared optical imaging magnetic nanoparticles myristoylated polyarginine
The authors would like to acknowledge Pamela Pantazopoulos (Martinos Center for Biomedical Imaging, MGH) for excellent technical support. This work was partially supported by K99 CA129070 to Z.M.
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