WUSM gets grant for work on microscopic capsules

(Republished with permission from the St. Louis Post-Dispatch. This article originally ran in the Science & Medicine section on Thursday, May 28, 2005)

By Eric Hand
Of the Post-Dispatch

Scientists at Washington University have been awarded big bucks to work on little things.

The National Heart, Lung, and Blood Institute has chosen the university as one of four national centers for medical nanotechnology. The program, headed by chemist Karen Wooley, comes with a $12.5 million, 5-year grant.

The award acknowledges that the university has the right expertise in both chemistry and medicine to develop microscopic capsules that would deliver medicine to specific places in the body.

The tailor-made drug delivery could lead to fewer side effects and faster healing for virtually any disease or trauma, from cancer to emphysema. Wooley cooks up the tiny dumpling- and doughnut-shaped nanocapsules that will carry drugs of therapeutic genes to specific parts of the body. The capsules are molecular cages so small they are almost beyond microscopic. Scientists measure the size of these new medical tools in nanometers. A human hair is about 1,000 nanometers wide.

Wooley is quick to praise the work of the 16 other program researchers who will figure out what to put inside the nanocapsule, how to get it to the right place and how to break apart the capsule at the right time.

Most drugs blanket the body. In the case of chemotherapy, the drug’s generality sometimes kills the person before it kills the cancer.

The key to the success of the nanocapsules is their specificity – delivering them only to trauma sites. That allows doctors to dose damaged areas in high concentrations without worrying about harmful side effects.

Researchers will add hair-like sensors to the nanocapsule. The sensors, strings of proteins called ligands, can recognize certain “alarm call” proteins produced by cancers or parts of the body that are in trouble.

Said Dana Abendschein, a Washington University biologist who studies blood vessels:

“There’s going to be a lock and key, the lock on the cancerous tissue or blood vessel containing a single protein. And the targeting ligand, which is essentially a key, on the nanoparticle that fits or combines with the receptor.”

The nanocapsule then has to break apart and release the drug (or therapeutic genes that would get damaged cells to produce new proteins). Some research has focused on breaking up the shell with bursts of light; other research has focused on using the slightly higher acidity of tumors and inflamed tissue to trigger the breakup. Once the drug is delivered, the nanocapsule would be metabolized or excreted.

The research will focus on trauma or disease to the heart, lungs and blood vessels. Abendschein said problems like emphysema, heart disease and thickened blood vessels are likely to be candidates.

Other researchers will figure out how to load the nanocapsule with dyes and radioactive substances so they can track its movement in the body. They’ve already lit up tumors in mice, proving that the nanocapsules can get to the right spot.

Wooley will continue to develop the packaging. She was excited when she and students discovered the doughnut-shaped package, which was described last fall in the journal Science.

“Now we have many more unique surfaces. We have an outside and inside.”

She said the doughnut could work in the reverse of other nanocapsules. Instead of bringing a drug to a damaged part of the body, the doughnut could capture something harmful – cholesterol, say – and carry it away in its hole.

Reporter Eric Hand
E-mail: ehand@post-dispatch.com
Phone: 314-340-8250

Copyright 2005 St. Louis Post-Dispatch, Inc.