Development and application of a dual-purpose nanoparticle platform for delivery and imaging of siRNA in tumors.
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.
Medarova
Zdravka
Z
Molecular Imaging Program, MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA.
Kumar
Mohanraja
M
Ng
Shu-wing
SW
Moore
Anna
A
D000818:Animals; D002232:Carbocyanines / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry; D005260:Female; D015316:Genetic Therapy; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D009369:Neoplasms / Q000235:genetics / Q000628:therapy; D010455:Peptides / Q000737:chemistry; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000032:analysis* / Q000737:chemistry / Q000627:therapeutic use; D019265:Spectroscopy, Near-Infrared / Q000379:methods*
C098793:CY5.5 cyanine dye; D002232:Carbocyanines; D004337:Drug Carriers; D010455:Peptides; D034741:RNA, Small Interfering; C015462:polyarginine