Happy Accidents Advance Versatility of Polymers for Nanomedicine

One of the most basic tenets of science is observation, an essential tool with the power not only to prevent but also in some cases redefine failure.

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A few years ago, a student in Texas A&M University chemist Karen L. Wooley's organic nanomaterials-based research laboratory was working to synthesize polymers in hopes of exploiting their protein-like properties. Instead of the anticipated result, he got an amazing one, unexpectedly discovering that they form gels, creating diverse opportunities from materials to medicine in the process.

"One of the most interesting things about research, I think, is when something surprising happens," Wooley said. "If the student is aware enough and observant enough to realize that what was observed was not expected and then follow through to characterize exactly why it happened and what the molecular structure is that led to that kind of behavior, then it can lead to entirely new research directions."

After determining precisely how and under what conditions these breakthrough gels formed, Wooley and her team moved on to the somewhat tedious task of refining them. Through further investigation, they learned the gels are based upon various amino acids and polypeptides -- the basic components of proteins and natural materials that, when synthetically linked together in unique sequences, can produce gel-like materials with fine-tuned, targeted properties.

Thanks to Wooley's expertise at scales 100 times thinner than a human hair, the versatility of polymers and happy accidents within her lab, the possibilities are highly adaptable and virtually limitless. For starters, imagine novel tissue engineering scaffolds capable of growing artificial tissue that can be customized to suit the repair or purpose needed. Then consider the next wave in orthopedics -- a growth-promoting, bone-like composite made from degradable plant-or-silica-based polymers instead of metal or other permanent irritants.

"Most of our nanoparticles are based on degradable polymers, and we wanted to shift from what were polyesters to polyamides to make protein-like synthetic particles," Wooley said. "As we were synthesizing those polymers, they gelled, which was completely surprising to us. We are looking into using these gels -- some of which are very stiff and some that are very flexible -- for tissue engineering scaffolds to grow artificial tissues that might then allow for implantation and treatment of various kinds of diseases, from artificial liver for transplant to skin-graft applications."

Wooley, a distinguished professor of chemistry and holder of the W.T. Doherty-Welch Chair in Chemistry since 2009, will be recognized next month as the first woman to receive the American Chemical Society Award in Polymer Chemistry, a prestigious accolade honoring outstanding fundamental contributions and achievements toward addressing global needs for advanced polymer systems and materials. Her 30-member research group spans seven distinct project areas and has an annual budget of more than $1.5 million, all dedicated toward some pioneering facet of organic polymer-based chemistry focused on creating new matter at the nanoscale level.

"My laboratory has always had a balance of fundamental basic science investigations that have allowed us to create materials that have never been created before and then to study their properties," Wooley said. "The process we use is going from an idea to a hypothesis to a design of a material that logically would meet that hypothesis. Once we understand how the materials behave and how their composition and structure relates to their properties, then we can define potential applications for those materials."

For the past eight years, Wooley has served as the director of a $33 million Program of Excellence in Nanotechnology (PEN) supported by the National Heart, Lung and Blood Institute. The award, which runs through 2015, supports nanoparticle-focused research expected to dramatically alter the future of medical practice with regard to detection, diagnosis and treatment of lung and cardiovascular diseases.

The collaboration involves five institutions and several directives, including two specific to lung injury and lung infection. To date, the researchers have produced promising results using targeted nanoparticles delivered via inhalation and packing an anti-microbial payload that dramatically reduces inflammation and improve treatment for lung infections. Once armed with the novel gels, Wooley anticipates exponential healing progress and potential impact on several related fronts, from cystic fibrosis to tuberculosis.

"We've found that when anti-microbial agents are loaded to our nanoparticles, they have a greater than ten-fold increase in the efficacy of lung-infection treatment, in comparison to the small drug alone and without the particle," Wooley said. "Moreover, by combining our gelatinous polypeptide materials with some of our nanoparticle anti-microbials, one can imagine additional possibilities in the design of specialized tissue scaffolds, for instance, for burn victims to prevent bacterial infection that would occur as the skin grows into the gelatinous material and replaces it."

Wooley cites the Texas A&M College of Veterinary Medicine and Biomedical Sciences and the Texas A&M Institute for Preclinical Studies (TIPS) as key reasons she chose to relocate her Washington University-St. Louis research group to Texas A&M. Both units offer a wealth of internationally renowned collaborators -- including Texas A&M biochemist and fellow PEN principal investigator Dr. James C. Sacchettini, an expert in tuberculosis and its treatment using crystallized proteins -- as well as resources and scenarios that will help move her lab's innovations from the bench to the marketplace, ultimately improving human and animal health and benefiting both industry and society.

"Pets develop the same types of cancers as people, including osteosarcoma," Wooley said. "These bone cancers then transfer into lung metastasis. We want to be able to apply our nanoparticles-based technologies to treat those lung and metastatic tumors using targeted therapeutic agents and then to conduct related studies at TIPS to evaluate their effectiveness. The initial step toward studies in canine pets is to confirm efficacy in a small-animal model, a mouse, which we are studying in collaboration with Dr. Dennis P. M. Hughes at MD Anderson Cancer Center, using expanded resources co-developed with Dr. Tiffany Gustafson in my lab and Dr. Mark Lenox at TIPS."

In addition to TIPS, the National Center for Therapeutics Manufacturing will provide resources for nanoparticle production and related materials for use in preclinical and clinical trials.

To learn more about Wooley and her research, visit http://www.chem.tamu.edu/faculty/wooley.

For more information on the Texas A&M Department of Chemistry, go to http://www.chem.tamu.edu.