Nanotech To Improve Health Care Delivery At The Molecular Scale

[Guest guest]

Nanotech To Improve Health Care Delivery At The Molecular Scale

http://www.medicalnewstoday.com/medicalnews.php?newsid=38078

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.

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 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 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.