Nanoparticles: target, track and treat breast cancer

Anticancer nanoparticles

Nanoparticles coupled to a fluorescent dye can be used to target tumour-specific molecules in breast cancer providing a way to track the particles by NIR spectroscopy, to enhance magnetic resonance imaging and to deliver an anticancer payload only to diseased cells.

Mohanraja Kumar, Mehmet Yigit, Guangping Dai, Anna Moore and Zdravka Medarova of the Molecular Imaging Laboratory at Massachusetts General Hospital and Harvard Medical School, in Boston, Massachusetts, explain how Iron oxide nanoparticles could be used in combined imaging of tumours and delivery of a therapeutic agent at the same time. They describe details of the system in the journal Cancer Research this month.

Nanoparticles on target

Medarova and colleagues, in work partly supported by the US National Cancer Institute, synthesised nanoparticle that bind to the tumour-specific molecule, uMUC-1. This structure is almost ubiquitous on the surface of human breast tumour cells, being present in 90 percent of cases. The team loaded the particles with a small interfering ribonucleic acid (siRNA) molecule, which can deactivate a specific gene, BIRC5, in the tumour cells. This gene is responsible for blocking normal programmed cell death, apoptosis, which allows the cells to replicate uncontrollably, the hallmark of cancer. When tested against breast cancer cells growing in culture, the team found that the nanoparticles had a significant impact on reducing expression of the BIRC5 gene.

In addition, the team added a third trait to their agent, a fluorescent dye (cyanine dye 5.5, Cy5.5) that would allow them to track the particles in the body. Moreover, given that the iron oxide nanoparticles are intrinsically superparamagnetic, they were also able to observe them using a magnetic resonance imaging, MRI, system. The team carried out tests, fluorescence imaging and MRI, and showed that the nanoparticles were rapidly taken up by the breast cancer cells in the laboratory. A follow-up experiment with human pancreatic cancer cells and colon cancer cells showed similar positive effects.

Not to dye for

The next step, of course, was then to test the nanoparticles in vivo. They injected the nanoparticles intravenously into a mouse model of human breast cancer. The drug was administered on two separate occasions, seven days apart. The MRI scans and fluorescence imaging revealed what the researchers hoped for, that the nanoparticles accumulated in the tumours in preference to healthy tissue and that concentrations stayed high over the course of the two-week experiment. Importantly, very few nanoparticles accumulated in the surrounding muscle tissue.

Examination of the tumours showed that the siRNA payload had caused a fivefold increase in apoptosis compared to control nanoparticles that carried a dummy nucleic acid payload. Critically, this demonstrates that the therapeutic effect of the nanoparticles is due to the siRNA rather than the tumour-targeting properties of the peptides (EPPT) on the nanoparticles themselves.

"RNA interference (RNAi) holds considerable potential as a molecular therapeutic tool due to its broad applicability and exquisite specificity," the team explains. Their work has now overcome main obstacles in the way of siRNA therapy in that achieving efficient delivery is commonly precluded by RNase degradation, interaction with blood components, and inefficient translocation across the cell membrane.

The modular nature of the new agent, which combines imaging, targeting and therapy means that it should be adaptable to other forms of cancer relatively easily, especially given that related iron oxides are already in clinical use. "Our strategy permits the simultaneous tumour-specific delivery of siRNA to tumours 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 tumour biology and therapy," the team concludes.

The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.