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In vivo imaging of siRNA delivery and silencing in tumors.
Nat. Med..Feb 25, 2007;13(3):372-7.
Medarova Z, Pham W, Farrar C, Petkova V, Moore A.
Massachussetts General Hospital/Massachusetts Institute of Technology/Harvard Medical School Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Charlestown, Boston, Massachusetts 02129, USA.
With the increased potential of RNA interference (RNAi) as a therapeutic strategy, new noninvasive methods for detection of siRNA delivery and silencing are urgently needed. Here we describe the development of dual-purpose probes for in vivo transfer of siRNA and the simultaneous imaging of its accumulation in tumors by high-resolution magnetic resonance imaging (MRI) and near-infrared in vivo optical imaging (NIRF). These probes consisted of magnetic nanoparticles labeled with a near-infrared dye and covalently linked to siRNA molecules specific for model or therapeutic targets. Additionally, these nanoparticles were modified with a membrane translocation peptide for intracellular delivery. We show the feasibility of in vivo tracking of tumor uptake of these probes by MRI and optical imaging in two separate tumor models. We also used proof-of-principle optical imaging to corroborate the efficiency of the silencing process. These studies represent the first step toward the advancement of siRNA delivery and imaging strategies, essential for cancer therapeutic product development and optimization.