Dec. 10, 2007 -- A specially designed nanoparticle affixed with a tiny magnet and a piece of DNA will free its drug cargo on demand when zapped with an electromagnetic field.
By offering a unique method for targeting therapies to disease, the approach could reduce the quantity of drugs necessary and also reduce unwanted side effects.
"You would like them not to release drug until they get to the tumor, and then once they get there, you want them to release the drug as soon as possible," said Geoffrey von Maltzahn, a Ph.D. student at the Harvard-MIT Division of Health Sciences and Technology.
The team, lead by associate professor Sangeeta Bhatia, described their technique in a recent issue of the journal Advanced Materials.
Soon after ingestion, most drugs begin leaking their chemicals into the body's blood stream, even if they are not yet near diseased tissue, such as a cancerous tumor. That can cause side effects and also make the drugs less potent.
Biomedical researchers have been exploring different ways for encapsulating drug compounds to reduce leakage. For example, one approach is to put the drug inside a polymer bead that slowly degrades and eventually exposes the drug to the tumor. Another method involves placing a particular molecule on the surface of the bead, so that it binds to a specific molecule in the tumor and then triggers the release of the drug.
But the system is not perfect.
"There is still leakage," said Warren Chan, a professor of materials science at the University of Toronto and an expert in developing nanostructures for biomedical applications. Furthermore, he said, "a lot of particles injected into the body get trapped in the liver and spleen and don't reach the target site."
The nanoparticles that the researchers developed look like a tiny bead with a tail. The bead has an iron oxide core and is coated with a polymer, but there is no drug inside. Instead, the molecule tows the drug behind it on a long rope made of DNA.
Molecules of hydrogen link the DNA to the bead and the drug to the DNA. These hydrogen bonds break when they are heated. And in fact, scientists can control the temperature at which the bonds break by adjusting the number of hydrogen molecules that make up the connection.
Bhatia and her team exploited that quality in the new technology.
The idea is that nanoparticles would be injected into the bloodstream. Engineered small enough to stay in the blood stream but big enough not to seep out blood vessel walls, they would eventually make their way to the tumor. Vessels leading to tumors are very leaky, and once the nanoparticles reached the diseased tissue, they would leak out into the cancer.
Particles with iron oxide show up on MRI machines and so doctors could watch the progress of the drug-towing beads. Once the nanoparticles reach the tumor, the doctor would zap them with a pulse of electromagnetic radiation. The energy would cause the iron in the bead's core to heat up, breaking the hydrogen bond and releasing the drug into the tumor.
A bead could potentially carry different kinds of drugs, too, each one engineered to release its cargo at a different temperature.
"This is one of the first papers I have seen that shows you can use the magnetic particles on the surface with DNA. It's that combination that makes it unique," said Chan.
But, said Chan, attaching the drug to the end of the DNA could alter its activity and the particles could still get trapped inside the liver or spleen on their way to the tumor.
"That's a major challenge in nanotech in general," said Chan.
The researchers have already demonstrated that the DNA tow ropes break when pulsed with the radiation. But those experiments were performed with the particles inside a gel-like substance. The next step is to test whether the particles will work inside cancer.
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