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FEATURE
Applying Nano-Scale Technologies to Make Big Ideas Possible
Grace Loo


Republic Polytechnic, Singapore There is an old proverb that says, “The bigger, the better”. However, advances in modern technology have helped scientists to prove that this saying may not always hold true. New advances in science have driven the development of nanotechnology, where the molecules and particles studied measure several millionths of a millimeter in length. Nanotechnology itself has been in existence for many decades, having been propelled into the limelight following the development and use of liposomes and the electron microscope in 1961.

Even within the field of nanotechnology, a number of different disciplines have formed as a result of the growth in this area of research. Bionanotechnology is one such discipline, merging together nanotechnology with biological research, thus allowing the use of nanotechnology to inspire and create systems that can be used to further research and development in biotechnology.

A number of different applications have also emerged from research into bionanotechnology. Some of its major applications include the development of diagnostic tools and devices, functional food and drug delivery systems, biosensors, and many other areas such as computing, information storage, and energy conversion. Powered by technological advances that enable the simulation, manipulation and assembly of materials one molecule at a time, bionanotechnology presents many scientific, technological, and commercial opportunities. Nanorobotics or molecular nanotechnology enable the creation of complex mechanical systems from the molecular level, through the use of DNA as a building material. Nanophotonics can potentially revolutionize harvesting of solar energy, as it utilizes layers of nanostructured thin films of photon-absorbing organic materials, which can be manufactured via solution-based methods, hence reducing production costs and enabling rapid mass-production. Protein nanoarrays are able to probe complex protein mixtures to study the details of protein reactions and cellular adhesion at a submicron scale, enabling diagnostic biomarkers to be detected and profiled at more sensitive levels than current technologies allow. This wide range of potential applications has driven the establishment of bionanotechnology as a growing field and industry worldwide.

The potential utility of bionanotechnology in functional food development also makes it a useful tool in the area of food and nutrition. Nanoscale modification of the food molecules may alter characteristics of the foods, such as taste, texture, and other attributes such as shelf life and stability. Furthermore, such changes can also result in improved water solubility, thermal stability, and bioavailability of certain ingredients which traditionally posed a challenge when incorporating them into their final food products. Bioactive ingredients that were once difficult to dissolve, such as phytochemicals like polyphenols and carotenoids, can now be mixed more easily into food products through the use of nanoemulsion-based delivery systems, which produce a class of extremely small droplet emulsions that can carry the polyphenols and carotenoids into the body. These result in mixtures that have significantly higher stability over traditionally unstable dispersions, compared to conventional emulsions and suspensions, and display higher kinetic and thermodynamic stability. The smaller sizes of these mixture droplets also allow the relevant phytochemicals to be transported through cell membranes in the body more easily, thus leading to greater bioavailability and concentration of the phytochemicals in the plasma.

Apart from improving the nutritional quality of foods, bionanotechnology also allows the design and development of functional foods to enhance nutrition for disease prevention and health promotion. Molecules such as drugs and vaccines can be incorporated as functional ingredients into foods through the use of encapsulation technologies as well. The application of bionanotechnology in the encapsulation of these drugs and vaccines has also opened up a variety of novel materials and methods for targeting and delivering these molecules to their intended sites. Biomaterials used for transport and encapsulation of these molecules in drug treatments or vaccinations typically possess several key characteristics. They should be non-toxic, biocompatible, and biodegradable, such as chitosan nanoparticles, which have been studied extensively for a wide range of uses.

The administration of active bio-compounds into the human body often requires the use of appropriate “vehicles”, which should be able to carry and deliver an effective concentration of the intact and active component to its desired target site in the human body. In the case of vaccine administration, if vaccines are administered orally, the unprotected antigens would easily be destroyed in a person’s gastrointestinal tract. However, bionanotechnology is helping to contribute to the formulation of vaccine delivery systems such as liposomes, microparticles, dendrimers, micelles, and nanoparticles, which can encapsulate and protect the antigen from hostile environments, such as the gastrointestinal tract. Moreover, many of these systems can maintain a sustained release of the antigen, therefore conferring better immune-stimulatory properties to the vaccine, and allowing it to evoke a more robust immune response. These encapsulation systems have also enabled the delivery of not just attenuated pathogen vaccines, but of DNA vaccines as well. These delivery systems also enable the protection and delivery of siRNA in RNA interference therapy, thus vastly increasing their bioavailability compared to traditional methods for RNA interference therapy.

On top of protecting against degradation in hostile environments in vivo, these encapsulation and drug delivery systems also allow the transport of drugs to specific sites within the body through conjugating the particles with targeting molecules, which are able to direct the transport of the drugs to their intended sites of action. This results in lower ‘collateral damage’ to other unintended cell and tissue types, hence reducing the severity of side effects for patients who take these drugs.

Such breakthroughs have powered the growth of nanomedicine, which is the medical application of nanotechnology in the development of useful research tools, advanced drug delivery systems, and novel disease treatment methods. These advances have helped to increase the solubility and dissolution rate of the drugs, allowing them to be absorbed more quickly and more extensively, thus enhancing their bioavailability. Active or passive targeting of the drugs through the use of targeting ligands has also helped to increase the specificity and efficacy of these drugs, resulting in lower collateral tissue damage and toxicity. Together, these improvements in nanomedicine have contributed to reducing overall drug dosages, as well as increasing the compliance of patients who take them.

This is especially beneficial in cancer therapy, where large doses of chemotherapy are traditionally required in the treatment of several forms of cancer. In one example, by attaching a compound from tea leaves to radioactive gold nanoparticles, a team of scientists recently created a new treatment for prostate cancer, which now requires significantly smaller doses than chemotherapy, and which does not inflict damage to healthy tissues in the body. In this treatment, the compound from tea provided the targeting ligand which directed the nanoparticle to its site in the tumor. The radioactive gold nanoparticles then very effectively destroyed the tumor cells. Inherently, careful consideration and design of the nanoparticles were key to the success of this new treatment, as well as any nanoparticle-based treatments. Firstly the gold nanoparticles were suitable for this treatment due to their favorable radiochemical properties, such as their very short half-life. Secondly, they had to be made to the correct size, as they could escape and spread if they were too small, but when made large enough could stay inside the tumor to treat it more effectively.

However, it has also been said that all that glitters is not gold. Although gold nanoparticles have garnered attention for the suitability of their use in many biomedical applications, their safety when introduced into living systems is still relatively unknown, and conflicting conclusions exist regarding their toxicity. Concern over the safety and toxicity of nanoparticles has opened up the new field of nanotoxicology, where the emerging safety, regulatory, and consumer issues related to the toxicity and effects of nanomaterials are studied extensively. Research has shown that gold nanoparticles may induce oxidative damage in human lung fibroblasts, and to overcome these adverse effects, coatings such as PEG need to be applied to their surfaces to improve the biocompatibility of these particles. Magnetic metal oxide nanoparticles such as iron oxide (magnetite) nanoparticles are often used as contrast agents in magnetic resonance imaging (MRI), drug delivery systems, and tracking. Their inherent properties such as the ability to penetrate cell and tissue barriers, combined with their high reactivity, may also increase their potential to induce oxidative stress through the generation of reactive oxygen species (ROS) within cells, potentially resulting in oxidative DNA damage or even apoptosis.

It is with these caveats in mind that we continue to proceed carefully, even while embracing advances in the various technologies. The articles in this issue highlight some of the discoveries and progress of bionanotechnology in food, medical, and even agricultural systems, which have indeed helped to address many challenges that are currently faced in these areas. Together with improvements in the analytical methods for the characterization of nanomaterials, bionanotechnology continues to offer the potential to scale greater (or smaller) heights in overcoming more challenges for these areas in the future.

About the Author

Grace Loo is an Academic Staff at the Republic Polytechnic in Singapore, where her major research interests center around antioxidants, animal health and nutrition, as well as the use of nanoparticles in drug and vaccine delivery.

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