Researchers have created an agent that holds potential as targeted therapy for breast cancer by combining an iron oxide nanoparticle, a tumor-targeting peptide and a therapeutic nucleic acid into one construct, and the new agent can be tracked easily in the body using standard MRI. The study was published in the October issue of Cancer Research.
Iron oxide nanoparticles offer a feasible tool for combined imaging and delivery of small interfering RNA (siRNA) to tumors. Zdravka Medarova, PhD, assistant professor of radiology at Harvard Medical School in Boston led the study. Medarova and her colleagues created the iron oxide nanoparticle to bind to a tumor-specific antigen uMUC-1, which is found on the surface of over 90 percent of human breast tumors, and delivered a synthetic small interfering RNA (siRNA) molecule designed to shut down a specific gene - BIRC5. BIRC5 blocks cell death in most tumors and is associated with the development of drug resistance.
The investigators also added a fluorescent dye, Cy5.5 for near-infrared optical imaging. The nanoparticle could be visualized with MRI as it was composed of superparamagnetic iron oxide.
When the nanoparticles were added to breast cancer cells growing in culture, they shut down the expression of the BIRC5 gene. Both fluorescence imaging and MRI showed that the nanoparticle was taken up rapidly by the cells. Subsequent experiments showed that this construct had the same positive effect on both human pancreatic cancer cells and colon cancer cells.
Based on these initial results, the investigators injected the nanoparticles intravenously into mice bearing human breast tumors. Both MRI and fluorescence imaging scans revealed that the nanoparticle accumulated preferentially in the tumors, and the levels remained high over the course of the two week experiment.
Furthermore, MRI could be used to quantitatively monitor nanodrug bioavailability in the tumor tissue throughout the course of treatment, according to Medarova and colleagues. Intravenous injection of the agent once a week over two weeks resulted in the induction of considerable levels of cell death in the tumors, translating into a significant decrease in tumor growth rate.
“Our strategy permits the simultaneous tumor-specific delivery of siRNA to tumors and the imaging of the delivery process. More generally, it illustrates the potential to apply this approach to many human cancer studies, including for basic tumor biology and therapy,” concluded Medarova and colleagues.