A dual imaging cancer probe
When it comes to cancer, it helps to have various detection methods. It’s even better if a cancer probe is simple to build and use yet provides powerful imaging and other capabilities. Now researchers from the Gwangju Institute of Science and Technology and from the Chonnam National University Medical School in Gwangju, both in the Republic of Korea, and from the University of Massachusetts Medical School in Worcester have demonstrated a probe with these characteristics.
Using a new nanoparticle coating method, they created a magnetic resonance and optical imaging cancer probe and demonstrated good results with passive targeting. “Other functional groups, including fluorophores, targeting ligands and even drugs, can be introduced onto the surface of it with ease,” said Sangyong Jon, an associate professor at the institute.
Superparamagnetic iron oxide nanoparticles are being investigated by many groups for use as magnetic resonance contrast agents (see previous story, for example). For in vivo imaging, the nanoparticles must disperse well, be biocompatible and have an antifouling property. Achieving that requires encapsulating the nanoparticles with a polymer and then cross-linking the polymer chains to make the coating tough enough for use.
Nanoaggregations of iron oxide nanoparticles (TCL-SPION) are coated with a polymerand functionalized with the dye Cy5.5 (left). A few hours after being injected into tumor-bearing mice, the nanoparticles have accumulated in the cancer and highlight it via magnetic resonance (middle) and fluorescence (right). Because of the polymer coating, the nanoparticles can be functionalized in a variety of ways. Reprinted with permission of the Journal of the American Chemical Society.
This has been done chemically for dextran-coated iron oxide nanoparticle chains. However, the researchers wanted to do the cross-linking and functionalization in fewer steps while eliminating any possibility of unreacted residual chemicals.
They already had developed an antibiofouling polymer, poly(TMSMA-r-PEGMA). The investigators cross-linked this polymer by heating it, a simpler process than the chemical technique. They modified it by adding a surface carboxyl group, creating poly(TMSMA-r-PEGMA-r-NAS).
Like the original, the new polymer could be cross-linked thermally, producing a stable coating. From there, noted Jon, it was easy to convert the carboxyl to other functional groups such as amines.
In a demonstration, the investigators functionalized thermally cross-linked polymer-coated iron oxide nanoparticles, attaching the near-infrared dye Cy5.5. The resulting nanoparticles had an average size of 31.9 nm (±4.6 nm). They administered the dual optical and magnetic resonance probe to tumor-bearing mice and imaged the animals a few hours later with a magnetic resonance scanner from GE Health Care of Milwaukee and an optical imaging system from Xenogen of Alameda, Calif. They found that the most intense fluorescence and the greatest change in magnetic resonance was evident in the tumor. A radiologist would have been able to identify the cancer, said the researchers.
Jon noted that the size and surface properties of the nanoparticles allowed this passive targeting to work so well. Future investigations will compare these results with those of active targeting, where ligands attached to the nanoparticles will help them accumulate in tumors. This comparison is important because, with the current passive targeting-based system — unlike with an active targeting one — it is hard to distinguish tumors from inflammation sites where new blood vessels, or angiogenesis, with leaky structures also are actively formed, Jon said.
Journal of the American Chemical Society, Oct. 24, 2007, pp. 12739-12745.
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