University in St. Louis has been chosen as a Program
of Excellence in Nanotechnology (PEN) by the National
Heart, Lung, and Blood Institute (NHLBI) of the National
Institutes of Health.
Karen Wooley, Ph.D., Washington University professor
of chemistry in Arts & Sciences, is principal
investigator of the Program, which NHLBI is funding
at $12.5 million for five years.
Three other PENs will also be established. Washington
University will serve as the administrative center
for this new nanotechnology initiative.
Collaborators with Wooley include 13 faculty members
from the Washington University School of Arts & Sciences
and the School of Medicine, plus one from each of
the University of California campuses at Berkeley
and Santa Barbara.
Nanotechnology involves the making of materials,
devices and systems of extremely small sizes, generally
between one and 100 nanometers. One nanometer is
one one-thousandth of a micron; a single strand of
human hair is between 50 and 100 microns, so a nanometer
is 50,000 times smaller than a human hair. Nanotechnology
enables researchers to take advantage of properties
and surface areas to create faster, more efficient
chips, sensors, pumps, gears, lasers, novel materials
and drug delivery systems.
According to Wooley, the prime focus of the Washington
University PEN is the development of nanoscale agents
that can be assembled, labeled, targeted, filled
and activated for eventual diagnosis and treatment
of various diseases relevant to NHLBI.
"Having this program is invaluable to the advancement
of nanotechnology because it brings together people
with crucial skills and expertise, allowing them
to cooperate with each other. This will allow nanotechnology
to coalesce into realized devices that are greater
than the individual contributions alone," Wooley
said. "The initiatives we'll undertake will provide
the leadership for nanoscience and nanotechnology
developments that can have clinical applications
through this century."
"The Programs of Excellence in Nanotechnology is
a vitally important research effort that will spur
the development of novel technologies to diagnose
and treat heart, lung, and blood diseases. The program
brings together bioengineers, materials scientists,
biologists, and physicians who will work in interdisciplinary
teams. By taking advantage of the unique properties
of materials at the nanoscale, these teams will devise
creative solutions to medical problems," said Elizabeth
G. Nabel, M.D., director of the National Heart, Lung,
and Blood Institute of the National Institutes of
Wooley, a synthetic organic chemist who has made
numerous important breakthroughs with nanoparticles
over the past decade, cited six specific aims of
- Preparation and assembly of programmed, integrated
- Application of nanostructures for imaging at
increased levels of sensitivity
- Imaging of gene expression by recognition of
messenger RNA (mRNA) transcription products
- Application of the nanostructures for therapy
- Cross disciplinary education and training of
medical and materials scientists
- Dissemination and translation of nanotechnology
As an example of how people in the PEN will collaborate
and rely on each other's skills, Wooley says to imagine
an injured vessel in the lung or cardiovasculature
as the target. With guidance provided by medical
experts on these diseases, Dan Schuster, Dana Abendschein
and Rob Gropler, nanoparticles that Wooley and her
lab members have been making for years called, shell
cross-linked nanoparticles (SCK), or other nanoscale
materials being developed in the laboratories of
Jean Frechet (UC-Berkeley) or Craig Hawker (UC-Santa
Barbara), will be used as carriers for diagnostic
imaging agents and also therapeutics.
Add a protective agent and then a permeation peptide
that allows entry into cells, and the nanomaterial
becomes more sophisticated. Incorporated into the
nanoparticle will be a chelater that will hold onto
copper 64 enabling collaborator Michael Welch, Ph.D.,
professor of radiology in the Washington University
School of Medicine, to image the injured tissue with
positron emission tomography (PET); once the nanoparticles
concentrate at the injury sight , they will light
up under PET imaging.
But how do the nanoparticles know how to find the
specific tissue? Enter John-Stephen Taylor, Ph.D.,
Washington University professor of chemistry, a synthetic
organic chemist who identifies a genetic sequence
made by the over expression of messenger RNA (mRNA),
a hallmark of tumor cells. Taylor can make a sequence
that binds to the cancerous mRNA, making a docking
site for the nanoparticles.
PEN collaborators Jean Frechet, Ph.D., of the University
of California-Berkeley, and Craig Hawker, Ph.D.,
of the University of California-Santa Barbara, are
working on a function that will trigger a breakdown
of the nanoparticles after they deliver their payload – a
drug or antiviral agent, for instance.
Wooley and her collaborators have been able to make
this nanosystem work in vivo, targeting cancer cells.
One prime goal is to use it to image gene therapy.
This is just one of many applications that Wooley
and her collaborators believe will come out of the
research performed in the Program, with emphasis,
ultimately, on translation to treat pulmonary and
acute vascular inflammation and injury in humans.
"We're excited by the many possibilities collaboration
such as this affords, and gratified that NHLBI has
chosen us," Wooley said. "We are going to make sure
that this technology is learned, shared, improved
and disseminated through publications and presentations