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.
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.
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.
The Future, Writ Small
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, firstname.lastname@example.org ,
David Kohn Ph.D.
Professor, Biologic and Materials Sciences and Biomedical Engineering
Martin Philbert, Ph.D.
Professor of Toxicology
Senior Associate Dean For Research, School of Public Health
Shuichi Takayama Ph.D.
Assistant Professor of Biomedical Engineering and Macromolecular Science and