Nanotechnology's potential for improving drug delivery, tissue regeneration and laboratory miniaturization is being explored by a diverse array of University of Michigan researchers.

A handful of these leading scientists from engineering, public health, dentistry and medicine discussed the promise of nanotechnology for oral health diagnosis and treatment on a special panel at the AAAS Annual Meeting on Feb. 17.

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.

Tissue regeneration

Panel co-organizer David Kohn, professor of biologic and materials science in the U-M Dental School and biomedical engineering in the College of Engineering, studies bone structure at the molecular level. In experiments that use tissue engineering to build bone and other mineralized tissue, Kohn said, "we use a process that's like nature's, but certainly not as elegant."

The nanoscale structure of bone is crucial to its ability to balance strength and light weight, Kohn explains. Many anti-osteoporosis drugs on the market today merely add mineral mass, without doing enough to duplicate the mechanical properties of bone. "Mass alone is not enough to impart fracture resistance," Kohn said. Kohn's recent work is exploring ways to control the mineral composition and structure of new bone.

Laboratory miniaturization: Reconfigurable cell adhesion substrates

A team led by Shuichi Takayama, assistant professor of biomedical engineering, has replicated the nano-scale features and stickiness of cell-adhesion molecules in a laboratory device. Studying how the surface of a cell interacts with adhesion proteins is key to understanding signal transduction, growth, differentiation, motility and cell death. But in vitro models are hard to come by.

Takayama's team has developed a substrate that can be split into parallel cracks and then lined with cell adhesion proteins to study cellular responses. The cracks may be tailored from 120 to 3200 nanometers, making them similar in size to the adhesion surfaces found in nature. The cracks may also be adjusted in situ to study changes in cell behavior.

AAAS Annual Meeting Advanced Seminar Oral Nanotechnology: Innovative Strategies for Disease Detection, Diagnosis, and Therapy 8:30 a.m. CST, Friday, Feb. 17.

Links
The Future, Writ Small
lifesciences.umich.edu/research/featured/050122/index.html

Michigan Nanotechnology Institute for Medicine and Biological Sciences nano.med.umich.edu/index.htm

News Media Contacts

James R. Baker MD
Ruth Dow Doan Professor of Biologic Nanotechnology, Professor of Internal Medicine
Director, Michigan Nanotechnology Institute for Medicine and Biological Sciences
Contact: Sally Pobojewski, pobo@umich.edu , (734) 764-2220

David Kohn Ph.D.
Professor, Biologic and Materials Sciences and Biomedical Engineering
(734) 764-2206
dhkohn@umich.edu

Martin Philbert, Ph.D.
Professor of Toxicology
Senior Associate Dean For Research, School of Public Health
(734) 763-4523
philbert@umich.edu

Shuichi Takayama Ph.D.
Assistant Professor of Biomedical Engineering and Macromolecular Science and Engineering
(734) 615-5539
takayama@umich.edu