Finding the Right Recipe

Researchers tailor magnetic nanoparticles for medical treatment & diagnosis. This new recipe could throw open new frontiers in imaging and drug delivery. 

Nanoparticles that possess magnetic properties offer exciting new opportunities for delivering drugs to targeted areas in the body, replacing radioactive tracer materials, improving the quality of noninvasive medical imaging, and producing ever-smaller data storage devices. But before these magnetic nanoparticles gain widespread use, scientists must learn to consistently control their key properties. 

Using only variations in chemistry and process conditions, researchers at the Georgia Institute of Technology have learned to precisely control the size and magnetic properties of one class of magnetic nanoparticles. Their goal is a "recipe book" other researchers could use to produce nanoparticles with exactly the right properties for different applications. 

"If you are going to produce these nanoparticles for large-scale use, you cannot guess at the conditions or rely on intuition," said Dr. John Zhang, Georgia Tech assistant professor of chemistry and biochemistry. "We are understanding the fundamental ways to control the properties of these particles, chemically manipulating the magnetic interactions at the atomic level. We want to control these properties through chemical means." 

Zhang presented his research team's latest findings at the 219th national meeting of the American Chemical Society on March 26 in San Francisco. 

Because each potential application for the magnetic nanoparticles requires different properties, the work is essential to their future use as carriers of drugs, tracers and MRI contrast enhancement agents. Also, it will provide insights to some key technical issues in high density information storage. 

For instance, each particle possesses certain magnetic orientations just as the north or south pole in a tiny magnet. Magnetic digital data bits in a computer hard disk have magnetic states similar to the nanoparticles. When the bits get smaller as the storage density increases, the magnetic state could become unstable. To avoid data loss caused by magnetic state change from simple temperature fluctuations, computer makers need to install a high enough magnetic energy barrier to stabilize the magnetic states. 

But for magnetic nanoparticles used in the body, physicians need particles with a low energy barrier to allow magnetic state to change constantly. Since magnetic opposites attract one another, the magnetic particles could potentially clump together, clogging blood flow. Rapidly changing the magnetic direction, therefore, would be essential to prevent the particles from aggregating. 

"We know that the energy barriers in these magnetic nanoparticles are due to atomic-level magnetic interactions," Zhang explained. "We want to make the connection between these atomic-level interactions and the macroscopic behavior that we want in these materials." 

The energy barrier between magnetic states -- which he likens to a hill that requires a certain amount of energy to climb over -- is proportional to the size of the particle as well as magnetic interactions. Zhang and his team have learned to control this energy barrier through chemical means. 

Another critical property is the size. Magnetic nanoparticles for in-vivo biomedical use must be small enough to avoid detection by the immune system, yet large enough to remain in the body long enough to be circulated through the bloodstream. 

And since magnetic properties vary by size, the particles must all be approximately the same diameter to ensure consistent properties. Zhang and his team have developed a statistical model to predict and control the size of the nanoparticles from synthesis process variables. They produce nanoparticles with size variations of less than fifteen percent, but hope to reduce that farther. 

Zhang and his team are also learning the surface characteristics of the particles that would help the nanoparticles get past the body's defense system. And by creating particular surface that would bind with certain types of cells, the nanoparticles could be used as magnetic tracers to detect cancers. 

Finally, the particles must be chemically stable enough so that they are not quickly broken down inside the body. 

Zhang and his team have used magnetic CoFe2O4 spinel ferrite nanoparticles, synthesized by a microemulsion method using sodium dodecyl sulfate as a surfactant to form micelles. There are many other chemical systems that can be used to produce magnetic nanoparticles, so a future goal is extend the understanding to other systems. That would provide additional flexibility and allow the cost of reagents to be factored into the equation. 

Potential uses for the magnetic nanoparticles include: 

Delivery of drugs to specific areas of the body. Magnetic nanoparticles containing drugs could be attracted to specific areas of the body by applying a magnetic field. Concentrating the particles in areas requiring treatment would enhance the therapeutic benefits while reducing side effects on other areas of the body. 

Improving the quality of magnetic resonance imaging. MRI sometimes does not provide enough contrast to enable good understanding of structures such as tumors. Addition of the magnetic particles could improve contrast between structures. 

Replacement of radioactive materials used as tracers. Radioactive materials are now attached to drugs as tracers. Physicians can then determine the location of these drugs by measuring variations in radioactivity. If the magnetic particles were substituted for the radioactive materials, physicians could instead measure magnetic variations, eliminating potential harm from radiation. 




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