Cristina Sabliov, Todd Monroe and Dan Hayes

While agricultural engineering has traditionally been employed for largescale monitoring, application and production, many new discoveries at smaller scales are improving our knowledge and application in agriculture. The LSU AgCenter Department of Biological and Agricultural Engineering has a diverse set of research programs integrating biology and engineering, with approaches that span dimensions from molecular systems to ecosystems and are equally broad in areas of implementation.

The application of nanotechnology to biological systems has great potential for improving health care, food science, homeland security and energy production. Nanotechnology can be thought of as the design and synthesis of functional systems at the molecular level, where sizes are measured in nanometers – a billionth of a meter. Nanotechnology has had profound effect on material science, from newer computer processors based on nanofabrication that run faster, to stronger and safer construction materials.

The field of biology is naturally ripe for nanotechnology implementation, as the building blocks of our genetic code and the proteins critical to all living systems are literally molecular machines. The AgCenter focus on bionanotechnology research includes developing nanoscale probes for genetic therapies and next-generation antimicrobials, and  designing and developing nanodelivery systems for vitamins, antioxidants, antimicrobials, DNA and drugs.

Because they are smaller than cells, nanostructures can penetrate deep into tissues through fine capillaries and generally are effectively taken into cells, allowing for efficient delivery of therapeutic agents to target sites. Nextgeneration, multi-functional nanostructures with controlled physical properties are being developed for encapsulating drugs and other bioactive components and releasing them in targeted tissues. The expected outcomes include reduced toxicity, improved cellular uptake and enhanced effectiveness of the delivered active agent for disease prevention and improved medical treatment.

The development of nanocarriers with enzymes to be reused in bioenergy conversion processes may greatly increase efficiency and affordability of renewable energy processes.

These nanobioengineering approaches in the AgCenter are funded by the National Science Foundation, National Institutes of Health and  the U.S. Department of Agriculture.

Food Nanotechnology  

The effect of nanotechnology on the food sector is expected to be wide-ranging. Researchers and industry experts envision better-quality and safer foods with enhanced nutritional and health benefits through nanotechnology. It is critical for food nanotechnology applications to demonstrate superior benefits that outweigh risks to ensure their acceptance by the food industry and the public. Limited information on the health and environmental risks associated with nanosize food materials has hampered immediate adoption in food applications and has triggered public interest and concern regarding the associated health risks of nanomaterials for food use. With the right science-based information on associated risks and benefits, however, the future of nanotechnology in foods is expected to be bright.

Different types of nanoparticle have been developed to deliver vitamins, antioxidants and other beneficial bioactive materials. The advantages of nanoparticles include protecting bioactive compounds from degradation, targeting and controlling the delivery of these materials and improving cellular uptake because of small particle size (Figure above).

Several AgCenter projects show that bioavailability and cellular bioaccessibility of vitamins and antioxidants are improved; in other words, more of the vitamin is available for the cell to use and is not lost. The human body does not synthesize most vitamins that are es sential for human health. Thus, these vitamins have to be obtained via the food and beverages we eat or by dietary supplements. Multiple issues – such as rapid degradation of vitamins during storage, handling and processing; low solubility of vitamins in the small intestine, and premature elimination – are responsible for decreased availability of the bioactive vitamins to cells.

Thus far, AgCenter researchers have shown that certain nanoparticles of controlled properties improve the uptake of vitamins such as vitamin E. This work is supported by a grant from the U.S. Department of Agriculture. Once fully developed and perfected, this technology can be extended to improve bioavailability of other vitamins (A, D, K) and components such as omega-3 fatty acids that are desired in food and dairy products. The stability and functionality of these nanostructures in a food matrix are dictated by the interaction between the nanoparticles and the foods themselves. Understanding the effect of nanoparticle properties is critically needed to better conceptualize, create and use multipletask nanoparticles that can interact with the food matrix and the body in a predictable way for better performance and improved outcomes in animal and human health.

Research on nanoencapsulation and delivery of bioactive components carried on by AgCenter researchers has the potential to become one of the pillars of emerging nanotechnology applications in the food industry. This work includes developing a highly skilled and educated workforce and creating broad nanotechnology platforms for launching new products and manufacturing technologies applicable to food and health.

Biomedical Nanotechnology

Nanotechnology provides a flexible and powerful platform to address infections and drug-resistant microbes. Infections that result from surgery represent a significant burden on limited health care resources. Many musculoskeletal surgeries, such as total joint replacement and trauma repair, involve the use of permanent or temporary implants that can provide vectors for infection. As the demand for such surgery increases from an aging population with traumatic injuries, the incidence of subsequent complications increases as well.

For example, the current rate of infection in total-knee-replacement surgery is between 1-2 percent. Infection in total joint replacements necessitates removal of all components, prolonged antibiotic therapy and repeat surgery. The cost of treating one infection averages approximately $30,000. Around 570,000 knee replacements are performed annually, and that figure is projected to increase to 3.5 million knee replacements by 2030.

Preventing or reducing the number of infections among these patients alone will significantly reduce the burden on the health care system and improve clinical results. Several research projects in the AgCenter address the development of new therapeutic or theranostic (combined therapeutic and diagnostic) treatments. Researchers are exploring ways of creating nanomaterial-based coatings for orthopedic implants to reduce rates of surgical-site infection and other associated complications. These coatings, composed of silver- and ceramic-based nanomaterials, can kill resistant bacteria in and around the implant, reducing infections rates and improving integration into the surrounding bone tissue.

A related project focuses on the development of a light-activated, theranostic nanoparticle delivery system. This system is composed of a magnetic nanoparticle (for imaging) modified with a very thin silver shell (providing light activation) and a unique steroidbased molecule that targets MRSA – Methicillin-resistant Staphylococcus aureus, a bacterial infection that is highly resistant to some antibiotics. When developed, this technology will allow doctors to simultaneously image the location of MRSA infections in the in the joint or bone by MRI and then selectively activate the antimicrobial only at the site of infection. The system, which is inactive without light, will allow patients to receive higher doses of antimicrobials, resulting in more rapidly cleared infections and better outcomes.

Another project using both delivery aspects like those shown in the figure and the medical applications described above is a project that uses light-sensitive chemistries to control the activity of DNA and RNA molecules. Manipulating these nucleic acids, which range in size from a few to several hundred nanometers long, is important because DNA and RNA function in a multitude of biological processes that govern who we are and how we feel.

Regulating DNA-dependent processes is central to the proper function of living cells, from single bacterial cells, to plant cells, to any of the trillion cells in the human body. The directed control of when and where DNA activity takes place is of interest both in clinical gene therapy trials, where DNA and RNA molecules are being tested as potential drugs, and also at the laboratory bench in developmental research or diagnostic assays.

Gene therapy is the production of therapeutic products by the cell’s own cellular machinery. DNA containing the code to produce these products must be introduced into the patient’s cells. Successful clinical gene therapy must both deliver these genes to the specific target cells and restrict this expression to only these target cells because off-target expression can yield unintended outcomes. One potential strategy for targeting expression of introduced genes is the non-specific delivery of “silent” genes followed by reactivation at selected sites with light exposure. An AgCenter team is working to chemically inactivate DNA by attaching photosensitive compounds that can be subsequently activated with light to restore the DNA function. This project’s technique could be a new way to target genetic therapies for cancer and other diseases so that the treatments are activated only in a tumor or other intended location.

New developments in nanomaterials are being used to protect therapeutic DNA and deliver it to intended cells, as well as to enhance the reactivity to light. Ultimately, this strategy may offer a new form of engineered control over many DNA-dependent processes, including hybridization-based biosensors, and the construction of complex DNA fabrics and nanomachines.

Cristina Sabliov, Associate Professor, Todd Monroe, Associate Professor, and Dan Hayes, Assistant Professor, LSU AgCenter, Department of Agricultural and Biological Engineering, Baton Rouge, La.

(This article was published in the summer 2011 issue of Louisiana Agriculture magazine.)