WUSTL awarded $18 million to treat heart, lungs with nanotechnology

An $18 million research program headed by Washington University School of Medicine in
St. Louis will research therapies and diagnostic tools for heart and lung diseases that use
nanotechnology.

The award, from the National Heart, Lung, and Blood Institute, will fund five years of research at Washington University and four collaborating
institutions: Texas A&M University, University of Texas Southwestern Medical Center, and the University of California, Santa Barbara and Berkeley.

Nanoparticles are 1 to 100 billionths of a meter in size. Scientists custom-engineer these tiny particles to deliver imaging agents or therapies, such as drugs, chemotherapies or genetic
material to specific targets, such as tumors, a particular cell type or sites of inflammation.

"Nanoparticles have several advantages over the small molecules typically used in imaging and therapeutics," says Michael Welch, PhD, professor of radiology and developmental biology and co-principal investigator. "Not only
can we load them with agents that deliver therapies to specific targets, we can include imaging agents that help us track both the nanoparticles and the therapeutic agent and change the surface of the particles to customize the amount of time they spend in the body."

The new initiative includes four principal research projects.

A synthetic chemistry group, led by Karen Wooley, PhD, of Texas A&M University, will
develop targeting molecules that allow nanoparticles to bind with receptors on the surfaces of cells involved in heart and lung diseases. Scientists target nanoparticles to different objectives in the body by customizing the particles' physical properties. This can include both adjustments of the materials nanoparticles are made of and alterations of the
crystalline and molecular configurations of the particles' components.

Wooley joins Welch as co-principal investigator of the overall project.

Scientists led by Carolyn Cannon, MD, PhD, of the University of Texas Southwestern
Medical Center, will develop nanoparticles as a means of treating patients with cystic
fibrosis. This inherited condition subjects patients to repeated, life-shortening lung
infections.

Cannon has shown that silver-based therapeutic agents act as antimicrobials and can treat
lung infections in mouse models. She has also found that delivering those treatments with
nanoparticles increases their effectiveness and reduces the required dosage.

Cannon and her colleagues will use the new funding to complete the preclinical research
necessary to begin testing this approach in humans with cystic fibrosis.

A third team of researchers, led by Steven Brody, MD, associate professor of medicine at
Washington University, will use nanoparticles to diagnose and treat various forms of acute
lung inflammation.

"Trauma and infectious diseases are the most common causes of this inflammation, but
there are others, including exposure to hazardous chemicals and additional genetic factors that we don't fully understand yet," Brody says. "We have some simple therapies, such as antibiotics, but to make real progress we need the flexibility and power that
nanotechnology can provide, both in diagnosis and therapy."

As proof of principle, Brody and his colleagues will be working to develop ways to use
nanoparticles to image and suppress the activity of nitric oxide synthase, an enzyme
commonly produced at high levels in inflammatory reactions in the lungs and airway.

The fourth group, led by Pamela Woodard, MD, professor of radiology at Washington
University School of Medicine, will work to develop nanoparticles to help physicians detect
early atherosclerosis.

Researchers have already created and tested nanoparticles that target a biological
indicator that appears very early in the plaque formation process. The indicator is a
receptor that blood cell vessels begin producing at higher levels even before plaques start
to stabilize.

Preclinical studies have shown such nanoparticle-based agents offer major advantages over the small-molecule agents more typically used to look for plaques. Scientists plan to test the nanoparticle-based imaging agents in Phase I clinical trials in the final years of the award.

"We want to find ways to stratify patients based on risk of heart disease, which could
potentially allow us to begin preventive treatments earlier in the disease process,"
Woodard says.

The award will also fund developmental projects evaluating receptors that can be targeted
with nanoparticles to image atherosclerosis and at ways to use optical imaging techniques
to track the behavior of nanoparticles.

A nanomaterials production core, led by Craig Hawker, PhD, professor of chemistry,
biochemistry and materials at the University of California, Santa Barbara, and director of
the UCSB Materials Research Laboratory, will provide facilities for the scaled-up
production of promising nanoparticle systems for pre-clinical studies. Facilities at Texas
A&M University and Washington University for additional nanoparticle production will
provide materials for use in preclinical and clinical trials.

A portion of the funds will support educational programs directed by Carolyn Anderson,
PhD, professor of biochemistry and molecular biophysics and of radiology at Washington
University School of Medicine. One goal of these programs, targeted to audiences ranging
from fourth graders to postgraduate students, will be to stimulate interest in careers in
medical nanotechnology development.

Provided by Washington University School of Medicine