Zdravka Medarova1, Mohanraja Kumar1, Shu-wing Ng2, Junzheng Yang2, Natasha Barteneva3, Natalia Evgenov1, Victoria Petkova4, Anna Moore1
1MGH/HST Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, USA; 2Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, Boston, MA, USA; 3Immune Disease Institute and Department of Pathology, Harvard Medical School, Boston, MA, USA; 4Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA
A powerful new approach for the directed regulation of gene expression utilizes the phenomenon of RNA interference. Here, we establish the feasibility of a novel technology centered around multifunctional magnetic nanocarriers (MN-NIRF-siRNA), which concurrently deliver siRNA to intact pancreatic islets and can be detected by magnetic resonance (MRI) and optical imaging. MN-NIRF-siRNA consists of superparamagnetic iron oxide nanoparticles (for magnetic resonance imaging), labeled with Cy5.5 dye (for near-infrared optical imaging), and conjugated to a DY547-labeled synthetic siRNA duplex targeting a model gene. Probe accumulation in the islets could be visualized by MRI and optical imaging. It resulted in a significant reduction in target gene expression levels. Our studies establish the feasibility of nanoparticle-based image-tagged siRNA delivery to pancreatic islets, using a novel multifunctional probe, which, in addition to its capability to deliver gene therapy in the form of siRNA, can also serve as an imaging contrast agent capable of detecting and following the fate of the probe in pancreatic islets.
Keywords