Iron oxide nanoparticles and derivatives for biomedical imaging and application in cancer diagnosis and siRNA therapy

Abstract

Our studies have focused on the application of imaging-capable nanoparticulate agents for the delivery of small RNA-based tumor therapy. One example includes magnetic nanoparticles (MN), which have traditionally been utilized as contrast agents for magnetic resonance imaging. The probes typically consist of a dextran-coated superparamagnetic iron oxide core (for magnetic resonance imaging), labeled with Cy5.5 dye (for near-infrared in vivo optical imaging), and conjugated to synthetic small interfering RNA (siRNA) molecules targeting model or therapeutic genes. We have explored the potential of these nanoparticles as delivery modules for small interfering RNA to tumors. Furthermore, we have investigated the feasibility of combining the imaging and delivery capabilities of these nanoparticles for the tracking of siRNA bioavailability. The versatile functionalization potential of MN has allowed us to control properties of the agents, such as uptake mechanism and target organ distribution. The tumoral accumulation of MNsiRNA results in a remarkable level of target-gene down-regulation. Repeated treatment with MN-siBIRC5, targeting the tumor-specific anti-apoptotic gene, birc5, leads to the induction of apoptosis in the tumors and an overall reduction in tumor growth rate. More recently, we have synthesized a second generation of nanoparticles, which combine the capability for high-resolution magnetic resonance imaging with detection by ultrasensitive surface enhanced Raman scattering.