Washington 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 Health (NIH).

Wooley, a synthetic organic chemist who has made numerous important breakthroughs with nanoparticles over the past decade, cited six specific aims of the Program

• Preparation and assembly of programmed, integrated nanosystems
• 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 developments

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 nationwide."