Artist’s conception of membranes forming on a gold ?lm with nanopores. Membranes are delivered asballoonlike vesicles that break open on contact to form ?at sheets. Green circles are proteins embedded in
the membrane that extend down into the nanopores. Biosensors can detect and characterize the interactions between membrane proteins and molecules such as antibodies.
Everything our bodies do depends on interactions that happen on a nanoscale, the realm of atoms and small molecules. Today, medicine is catching up.
At the University of Minnesota, nanomedicine researchers are pushing forward with projects like new drug-delivery technologies and better screening of potential drugs.
April 29, 2013
Feature
Nanoparticles against cancer
In cancer biology, for example, mechanical engineering professor John Bischof, chemistry associate professor Christy Haynes, and radiology professor Michael Garwood are out to deliver nanoparticles of iron oxide to tumors and kill them with heat while sparing healthy tissue.
“We want to get the temperature of the nanoparticles above 45 degrees C [113 F],” says Bischof, whose expertise is heating measurements.
This is possible by applying alternating magnetic fields around the nanoparticles inside living tissue. The applied fields make the particles’ magnetic fields flip direction quickly, or they roll the particles back and forth, creating friction. These motions heat the particles within tumor cells that contain them, but not normal cells, which don’t.
Ideally, the team would inject enough iron oxide into a tumor to achieve more than 1 milligram of iron per gram of tumor tissue. It is important to know how many of the nanoparticles have been absorbed by a tumor so as not to overtreat.
“Unfortunately, clinical imaging like ultrasound or computed tomography [CT] can’t accurately measure iron concentrations in that range,” Bischof says.
However, at the U’s Center for Magnetic Resonance Research, Garwood has developed SWIFT, a new technology that can. At present, no other imaging technology is capable of this, Bischof says.
To improve stability and heating properties, Haynes applies coats—10-20 nanometers thick—of a special “mesoporous” silica. This silica naturally contains pores, into which molecules of anti-cancer drugs can be added for a one-two punch.
Dartmouth College researcher Jack Hoopes depends on this work as he, along with physicians, move toward bringing iron oxide thermo-therapy to patients. Clinical trials with breast cancer patients are scheduled to begin this year.
Are they toxic?
Nanomedicine also concerns the toxicity of nanoparticles. When inhaled in quantity, they can be harmful. But what if they’re ingested and get into the bloodstream?
Christy Haynes has tested commonly used nanoparticles—made from silica, titanium, gold, and silver—for toxicity to several types of cells from the immune systems of lab animals and humans.
“With the four types of particles, we almost always see 80 percent viability of the cells,” she says. In other words, the cells held up pretty well. Haynes hopes to learn if this result will apply to other cells with similar functions. She also wants to answer big questions like: How long do nanoparticles last in the body? and How are they excreted?
Drug screening
If a drug is to elicit some response from a cell, it first must interact with a protein “receptor” embedded in the cell’s outer membrane. A good candidate drug is one that interacts strongly, but measuring the strength of interactions is inefficient because most tests in use only tell whether or not an interaction occurs.
But that’s about to change.
“We’re developing optical sensors to study how proteins interact with molecules,” says Sang-Hyun Oh, an associate professor of electrical and computer engineering. “Membrane proteins are the main targets.“
Oh and his colleagues have developed a way to fabricate ultrathin gold films containing nanoscale pores in a precise array. In experiments, they lay a membrane containing receptors over a film, with the receptors protruding from the membrane both downward into the pores and upward. Next, they add a candidate drug to be tested.
Under laser light, electrons in the gold atoms resonate and funnel the light down the pores and into a detector. This response is very sensitive to how a drug candidate interacts with a receptor.
Oh and his team created the instrument that measures the interaction strength. They are collaborating with Mayo Clinic neuroscientists who have developed antibodies to potentially treat multiple sclerosis by restoring neurons’ myelin sheaths, which the cells need to function normally.
“With rodents, we found that the antibodies attached to membranes of [myelin-forming cells] and triggered them to initiate repair,” says Oh.
Without Oh’s group, the Mayo Clinic scientists would have to rely on costly, inefficient testing of the antibodies they produce. Clinical trials with MS patients will begin soon.
Tags: College of Science and Engineering, Academic Health Center
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