PROVIDENCE, R.I., May 27, 2008 -- The smallest magnetic nanoparticles created to date can be sent on such seek-and-find missions for tumor cells and emit signals MRI scans can detect.
Brown University chemist Shouheng Sun and a team of researchers have created peptide-coated iron oxide nanoparticles, billionths of a meter "big." They injected the particles into mice and tested their ability to locate a brain tumor cell called U87MG.
The team concentrated on the nanoparticles' size and the thickness of the peptide coating, which ensures the nanoparticle attaches to the tumor cell. (With a thinner coating, the particles also emit a stronger signal for the MRI to detect.) In the process, the researchers discovered that the RGD peptide coating binds almost seamlessly to the U87MG tumor cell.
How an RGD peptide-coated iron oxide nanoparticle binds with an integrin-rich tumor cell. Bottom left: An MRI of a mouse with the implanted U87MG tumor (red circle). At right is an optical image that reveals iron oxide nanoparticles (blue) amassed in the tumor area (pink). (Image: Jin Xie, Brown University)
The coating, while integral to the nanoparticles' attachment to the tumor cell, is also crucial to establish the "signal-to-noise" ratio that a MRI uses. The thinner the coating, the stronger the emitted signal, and vice versa. Sun's team outfitted the nanoparticles with a two-nm-thick peptide coating -- 10 times thinner than the coating available in popular MRI contrast agents such as Feridex.
"Sun's nanoparticles are like having a 50,000-watt radio transmitter versus a 150-watt station," the university said in a statement. "It's easier for the MRI to 'hear' the stronger signal and to hone in on the signal's source."
Nanoparticles are important in MRI detection because they enhance what scientists refer to as the "contrast" between the background, such as water molecules in the body, and a solid mass, such as a tumor. Magnetic nanoparticles can be especially helpful in locating cancerous cell clusters during MRI scans. Like tiny guide missiles, the particles seek out tumor cells and attach to them. Once they bind themselves to these cancer cells, the particles operate like radio transmitters, greatly aiding MRI's detection capability. MRI scans use pulses of magnetic waves and gauge the return signals to identify different types of tissue in the body, distinguishing bone from muscle, fluids from solids, etc.
The trick for researchers is to create a nanoparticle small enough to navigate through the bloodstream and reach the diseased area. Bigger particles tend to stack up, creating the circulatory system's version of a traffic jam. Sun's team developed a nanoparticle about 8.4 nms in overall diameter — about six times smaller than the size of particles currently used in medicine.
"We wanted to make (the nanoparticle) very small, so the body's immune system won't recognize it," Sun said. "That way you let more particles interact with and attach to the tumor cell."
He said the team plans to test the particle's ability to bind with other tumor cells in further animal experiments.
The National Cancer Institute, part of the National Institutes of Health, and the Department of Energy's Experimental Program to Stimulate Competitive Research (EPSCoR) funded the research.
The results are published in the Journal of the American Chemical Society. Brown graduates students Jin Xie, Chenjie Xu and Sheng Peng collaborated on the research, along with Professor Xiaoyuan Chen and his associates from Stanford University.
See also: "Nanoparticles as Beacons"
For more information, visit: www.brown.edu
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