Drug delivery

To help get the most potent anti-cancer drugs off the shelf and into the clinic, U-M researchers are looking at two nanotechnology approaches to precisely deliver drugs and visualize individual cells.

One system is a star-shaped synthetic molecule called a dendrimer, and the other is a tiny plastic bead called a PEBBLE.

A dendrimer is a star-shaped synthetic molecule that can be as small as three or four nanometers in diameter, about the size of a single molecule of hemoglobin in a red blood cell. That means it is also fine enough to slip through the walls of blood vessels and get inside cells.

James R. Baker Jr. is leading the dendrimer projects as director of the Michigan Nanotechnology Institute for Medicine and Biological Sciences, with support from the National Cancer Institute, NASA, and the Bill and Melinda Gates Foundation.

The ends of a dendrimer's many branching arms can be studded with molecules that bind to specific receptors on the surface of cancer cells. Other arms of the molecule can carry chemicals to mark or even kill the target cells. Injected into the bloodstream, dendrimers converge on cancer cells, then actually enter the cells. There, they deliver the drugs that kill cancer cells. In preliminary animal studies, drugs appear to be 50 to 100 times more effective with this sort of direct delivery, Baker said.

A group led by toxicologist Martin Philbert and biophysicist Raoul Kopelman is working with tiny plastic beads called PEBBLES-probes encapsulated by biologically localized embedding.

Sized at 20 to 600 nanometers, PEBBLES can be coated with targeting molecules and used as a very precise contrast agent for imaging and drug delivery. Once they reach their goal, sound or light can trigger them to carry out their mission. In some cases, the killer agent can be something as simple as reactive oxygen, says Philbert, a professor of toxicology and senior associate dean for research in U-M's School of Public Health.

Though the PEBBLEs group has done work to get the tiny balls inside cells, including using a gene gun that blasts them like little bullets and attaching them to liposomes and letting the body's own fats provide the transportation, Philbert notes that penetration isn't always necessary to get the medical benefits. He says the tiny balls latched on to the outside of selected cells can deliver "killer oxygen" on cue to kill off the cell without penetrating it.