Pulling No Punches

Will nanomedicine and other tech advances knock out devastating diseases?

Font Size

Article body

When it comes to biomedical engineering research and instruction, Auburn University’s Samuel Ginn College of Engineering is emerging as a leader on the forefront of finding solutions and cures to some of the world's most serious human health issues. Auburn Engineering faculty members are collaborating across campus and disciplines in this effort, uncovering and discovering many diagnostic and delivery systems that will change the way we look at once grim diagnoses.

Fighting cancer

Cancer. It affects almost all of us. Whether it’s you personally, a family member or a friend, cancer is ravaging our country at an astounding rate. According to the American Cancer Society, more than 1.8 million new cases will be diagnosed in 2020, and more than 600,000 people will lose their battle with the disease this year.

This terrible trend must stop.

Here at Auburn University we are engineering a cure. Not only is our cutting-edge research attacking cancer at the source, but it’s also helping to diagnose and better treat the debilitating effects of this disease.

Through collaborative efforts from Samuel Ginn College of Engineering professors Dr. Allan David and Dr. Elizabeth Lipke, along with researchers in the College of Veterinary Medicine, the Harrison School of Pharmacy and the Department of Nutrition, Dietetics and Hospitality Management, the race for a cure is taking place right here at Auburn.

David, a faculty member in the Department of Chemical Engineering, oversees a nanoparticle and nanocomposite lab that is focused on highly selective drug targeting to enhance cancer therapy.

Part of David’s research targets cancer cells in a highly selective way so that the therapy goes to the diseased site and does not interfere with healthy cells in the rest of the body. For example, achieving a therapeutic concentration in a tumor could require gram-level doses of a drug that distributes through the entire body.

The “smart nano” approach places the drugs where they can be effective. They are contained within nanoparticles and nanocomposites that target and stick to the cells that need to be treated. It’s an approach that will allow for much greater treatment efficacy at lower delivery doses and a resulting reduction in side effects.

David’s research also holds great promise for insulin therapies in diabetics, since insulin cannot be delivered orally and must, therefore, be injected.

The benefits of nanotechnology will ultimately lead to what is called personalized medicine—targeted therapies that reduce dosage amounts and frequency, which results in better treatment at lower cost. It is also anticipated that patients treated in this way will recover more quickly, and become productive again in a shorter amount of time.

Lipke, a faculty member in the Department of Chemical Engineering, and her team are developing 3D in vitro cancer models for use in drug-testing applications. Employing a range of metastatic and non-metastatic cancer cell lines, they are encapsulating the cells in hydrogel materials to create tissue-engineered "tumor microspheres" and "tumor millibeads."

Using 2D monolayer cultures and self-aggregated 3D tumor models, researchers and scientists are unable to capture key features of the complex in vivo tumor, severely limiting their ability to obtain clinically-relevant data in cancer drug-testing applications. In addition, the information acquired from these models, including identification of new cancer drug candidates, does not reflect the actual response seen in animal testing and human trials.

By using novel fabrication techniques, the tissue-engineered tumor models developed by Lipke and research team members reproduce native tumor characteristics not emulated by traditional models. Importantly, these techniques can be used to form engineered tumors with multiple contributing cell types or from non-self-aggregating metastatic cancer cells. Models are formed through the encapsulation of cancer cells within poly(ethylene glycol)-fibrinogen (PEG-Fb) hydrogels. The tumor microspheres support long-term 3D culture of the cancer cells and, by more accurately mimicking the properties of tumors within cancer patients, results could provide a platform for identifying more effective candidate drugs for animal and clinical testing. The model will not only help medical experts more carefully examine the tumor microenvironment, which is known to play a significant role in the malignant progression of cancer, but will also aid in the study of tumor growth for breast, prostate and colon cancer.

Rapid Response

In the fight against cancer and autoimmune diseases, time is often a clinician’s worst enemy.

Having real-time data on the health and function of a patient’s immune system is critical to treating these diseases. However, one of the main diagnostic tools in use today, the enzyme-linked immunosorbent assay, must be sent to a lab and will take hours to days for results to return.

By then, the dynamics of the immune system may have completely changed, leaving the clinician to make treatment decisions based on outdated information.

Dr. Pengyu Chen, assistant professor of materials engineering, is aiming to change that by developing optofluidic nanoplasmonic biosensors for rapid analysis of the immune system. The research, supported by a $1.9 million National Institutes of Health grant, seeks to better understand and measure cytokines—tiny proteins vital to signaling between cells—for rapid diagnostics.

“The ultimate goal is to develop a biomedical device based on nanoparticles that we can use to take one droplet of the patient’s blood, and in a short period of time, we can accurately tell if the patient’s immune system is healthy or not,” Chen said.

The research project has three primary goals: to integrate nanoplasmonic structures into biosensors for higher performance and faster response times; to fabricate microfluidic devices for target cell isolation and on-chip measurements and analysis; and to develop nanoplasmonic ruler biosensors—two nanoparticles linked with one DNA—to visualize cytokines secreted from a single immune cell and eventually map out its secretion profile. Previous research suggests that measuring cytokine-based immune fingerprints provides useful information related to infectious diseases, cancer and other diseases.

“We are trying to provide real-time feedback of the immune system for personalized immunomodulatory therapies,” Chen said. “Currently, there is no technology that can serve as a real-time diagnostic tool to tell if the dosage of a therapy is good or not. Our hope is that we can develop a technology that can be used at bedside or a point-of-care device so that physicians can make decisions based on these measurements more quickly and accurately and then potentially change the outcome of the therapeutics.”

Resonance of Research

It was a big deal when Auburn got only the nation's third actively shielded whole-body 7 Tesla MRI in 2012, figuratively and literally. Workers had to lift it out of the crate with a crane. It took a little while.

Dr. Tom Denney, professor in electrical and computer engineering and director of the Auburn University MRI Research Center, didn’t mind.

Still just one of just three 7 T machines in the South, the $8.5 million investment allowed Denney’s team and others game-changing access to dimensions of detail once unimaginable in brain imaging. Its installation was the final step in implementing the $24-million research center’s mission: saving lives.

"This is not engineering for engineering's sake," Auburn University trustee and former CEO of Alabama Power Company Charles D. McCrary, '73 mechanical engineering, told reporters at the 2010 groundbreaking for the 45,000-square-foot facility.

Turns out, it was for JoJo's sake.

Though intended primarily for cognitive neuroscience, the 7 T’s most recent, high-profile success story may be a breakthrough treatment for GM1 gangliosidosis, a devastating genetic nerve disease that affects around one in 100,000 children. But for one of those children, it may no longer be a death sentence.

In May, 10-year-old JoJo, who needs help to stand and even speak, began the first in-human GM1 gangliosidosis gene therapy trial, developed in large part through a collaboration between the MRI Research Center and the College of Veterinary Medicine’s Scott-Ritchey Research Center.

The results have so far put smiles on the faces of everyone involved.

"She's actually gotten slightly better,” said Dr. Doug Martin, a professor in the Scott-Ritchey Research Center. “It was thought that once the disease reached a certain point, you wouldn’t be able to recover any function, but she has. Of course, that could all end tomorrow, but right now she’s doing well.”

For several decades, Martin has studied feline GM1 gangliosidosis in cats, which manifests identically as the human variety of the disease. If ever a potential gene therapy could be developed, he suspected a cat would be the perfect model. So did Dr. Cyndi Tifft, a geneticist at the National Human Genome Research Institute in Bethesda, Maryland, who in 2006 began a natural history study of 35 children with GM1 gangliosidosis.

"She was doing cutting-edge research on biomarkers of disease progression in human patients with gangliosidosis, and she wanted to test the same biomarkers in cats," Martin said.

The two joined forces 15 years ago. But in 2012, now with access to one of only a handful of 7 T MRIs in the country, the magnitude of their research increased exponentially.

“I almost couldn’t believe we’d made the investment,” Martin said. “It was such a tremendous step forward for all of our research on animal models and human patients. It was really amazing because Auburn had not traditionally put a lot of emphasis on biomedical research, and then the 7 T showed up.

“We can watch the progression of gangliosidosis and the progression of the therapeutic results in a live animal without having to euthanize the animal and take a sample post-mortem. I think there’s only one or two other vet schools with access to a 7 T.”

Denney, who has helped train Martin’s laboratory team on how to use the center’s crown jewel, said the increase in insight into brain chemistry allowed by 7 T technology can’t be overstated.

“The strength of the magnet provides a much, much higher resolution,” he said. “We can see things in the brain now that we could never see before. We use it to measure different metabolites in the brain, which are indicators of the response to therapy or disease progression. It gives us much clearer, more accurate data that we can trust much more.”

The U.S. Food and Drug Administration trusted it, too, greenlighting clinical trials—and JoJo’s chance for a future—thanks directly to the gene therapy vector Martin and colleagues helped develop and test with the 7 T.

"We probably have used the 7 T more than any other outside group," Martin said. "That kind of tells you how important it is to what we're doing. It’s a big part."

Auburn University is a nationally ranked land grant institution recognized for its commitment to world-class scholarship, interdisciplinary research with an elite, top-tier Carnegie R1 classification and an undergraduate education experience second to none. Auburn is home to more than 30,000 students, and its faculty and research partners collaborate to develop and deliver meaningful scholarship, science and technology-based advancements that meet pressing regional, national and global needs. Auburn's commitment to active student engagement, professional success and public/private partnership drives a growing reputation for outreach and extension that delivers broad economic, health and societal impact. Auburn's mission to educate, discover and collaborate drives its expanding impact on the world.