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Geometrical Confinement of Gadolinium-Based Contrast Agents in Nanoporous Particles Enhances T1 Contrast

A porous, disk-shaped "nest" for nanotubes may help magnetic resonance imaging become better than ever at finding evidence of cancer if the results of research led by investigators at Rice University are any indication of future success.

This research team, which also included colleagues from other Texas Medical Center institutions, as well as those in Colorado, Italy and Switzerland, have developed a general method for trapping paramagnetic nanoparticles inside a silicon particle that, when injected into a patient's bloodstream, would make the nanoparticles up to 50 times more effective at spotting tumors or other signs of disease. Paramagnetic contrast agents "light up" damaged tissue in the body in images produced by MRI instruments.

"Making MRIs better is no small matter," said Lon Wilson, one of three senior co-authors of the research paper published in the journal Nature Nanotechnology. The other senior co-authors include Mauro Ferrari, from the Methodist Hospital Research Institute, and Paolo Decuzzi, of the University of Texas Health Sciences Center at Houston. Drs. Ferrari and Decuzzi are members of the Texas Center for Cancer Nanomedicine, one of nice Centers of Cancer Nanotechnology Excellence funded by the National Cancer Institute's Alliance for Nanotechnology in Cancer.

In 2007, 28 million MRI scans were performed in the United States, and contrast agents were used in nearly 45 percent of them. "MRI is one of the most powerful medical tools for imaging, if not the most powerful," said Dr. Wilson. "It's not invasive, it's not ionizing harmful radiation, and the resolution is the best you can get in medical imaging." MRI's main limitation is its sensitivity. "So anything you can do to improve performance and increase sensitivity is a big deal -- and that's what this does."

A nano-sized slice of silicon shaped like a hockey puck served as a delivery device for contrast agents in the study. Pores that were mere nanometers long and wide were created in the discs, called silicon microparticles, or SiMPs. Three types of contrast agents were drawn into the pores. Magnevist, a common contrast agent used worldwide, was one; the others were gadofullerenes and gadonanotubes. All three of these contrast agents chemically sequester the toxic element gadolinium to make it safe for injection.

MRIs work by manipulating hydrogen atoms in water, which interact and align with the applied magnetic field from the instrument. The hydrogen atoms are then allowed to return to their original magnetic state, a process called relaxation. In the presence of the paramagnetic gadolinium ion, the atoms' relaxation time is shortened, making these regions brighter against the background under MRI.

SiMPs are small and when they trap both water molecules and bundles of nanotubes containing gadolinium, the protons appear much brighter in an MR image. Because SiMPs keep their form for up to 24 hours before dissolving into harmless silicic acid, the molecules can be imaged for a long time. The trick, though, is getting them to places in the body that doctors and technicians want to see. Wilson said SiMPs are designed to escape the bloodstream, where they leak and aggregate at the sites of tumors and lesions. "Spherical particles, at least in mathematical models, flow down the center of the vasculature," he said. "These particles are designed to hug the wall. When they encounter a leaky area like a cancer tumor, they can easily get out."

The encapsulation within SiMPs enhanced the performance of all three contrast agents, but SiMPs with gadonanotubes (carbon nanotubes that contain bundles of gadolinium ions) showed the best results. "The performance was enhanced beyond what we had imagined," he said. SiMPs may also be functionalized with peptides that target cancer and other cells. SiMPs that contain contrast agents and anticancer agents could potentially be tracked as they home in on tumors, where the drugs would be released as the silicon dissolves.

This work is detailed in paper titled, "Geometrical confinement of gadolinium-based contrast agents in nanoporous particles enhances T1 contrast." An abstract of this paper is available at the journal's website.

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