In 1966, movie-goers were treated to the release of a film called Fantastic Voyage, a Cold War science fiction thriller about a scientist who is nearly killed in an assassination attempt.
As he hovers between life and death, a medical team is reduced to microscopic size then ventures into his body to carry out the delicate brain surgery needed to save his life. Starring Stephen Boyd, Raquel Welch and Donald Pleasence, it was an entertaining romp and all based on fantasy. Little people journeying through the human body? All very Hollywood but it could never really happen, yes? Well, yes. And no. We may not be able to shrink people, probably never will, but the concept that ‘small is beautiful’ is interesting medical science more and more. Researchers can increasingly see the benefit of the emerging science of nanotechnology as a way of carrying out previously invasive procedures and also adding immeasurably to their knowledge of the human body. Nanotechnology is the industry in which tiny computers called nanites work throughout whatever object into which they are inserted, operating at the molecular level.
The concepts behind modern nanotechnology were first given international exposure by physicist Richard Feynman in 1959, who gave a speech in which he talked about how we would one day be able to manipulate atoms and molecules and craft them into whatever we wanted them to be. He went on to discuss the possibility of creating extremely small machines that would serve as tiny tools. Since then, the idea has taken shape and nanotechnology – the science of the small – is coming of age and is capable, say medical scientists, of being used extensively for everything from replicating cells to analysing broken bones.
There are already some exciting examples of its application. Take the work being done at Harvard University in the United States where scientists have designed the first large DNA crystals with precisely prescribed depths and complex 3D features, which they say could create revolutionary nanotechnology devices. DNA has potential as a platform that could support new nanodevices in computer science, microscopy, biology and researchers have been working for twenty years to coax DNA molecules to self-assemble into the precise shapes and sizes needed in order to make the nanotechnology work. Key to that that has been designing large DNA crystals with precisely prescribed depth and complex features, something now achieved by a team at Harvard’s Wyss Institute for Biologically Inspired Engineering.
The team built 32 DNA such crystals using a ‘DNA–brick self–assembly‘ method, rather similar in concept to Lego, which was first demonstrated in 2012 when they created more than 100 3D complex nanostructures about the size of viruses. The new crystal structures are more than 1,000 times larger than those early structures, closer to a speck of dust in size, which qualifies as large in the world of DNA nanotechnology. William Shih, Ph.D., who is co–author of the study and a Wyss Institute Founding Core Faculty member, as well as Associate Professor in the Department of Biological Chemistry and Molecular Pharmacology at Harvard Medical School and the Department of Cancer Biology at the Dana-Farber Cancer Institute, is excited by the potential.
He said: “My preconceived notions of the limitations of DNA have been consistently shattered by our new advances in DNA nanotechnology. DNA nanotechnology now makes it possible for us to assemble, in a programmable way, prescribed structures rivalling the complexity of many molecular machines we see in Nature.” “My preconceived notions of the limitations of DNA have been consistently shattered by our new advances in DNA nanotechnology.” William Shih, Ph.D. Associate Professor, Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School
Nanotechnology’s role in delivering drug treatments
The development of DNA technologies is just one possible application for nanotechnology. Scientists are also realising its potential for the delivery of drugs. In America, LayerBio, which develops drug delivery products for ophthalmology and wound care applications, has received a $150,000 research grant to support development of its nanoparticle-based glaucoma therapy, from the National Science Foundation.
Figure 1: Developed by Wyss Institute Core Faculty member Peng Yin and his team, the DNA-brick self-assembly method uses short, synthetic strands of DNA that bind and interlock like Lego® bricks. Credit: Wyss Institute at Harvard University.
Glaucoma is the leading cause of irreversible blindness worldwide. In the United States alone, an estimated 2.2 million people suffer from it and the typical first-line treatment for glaucoma is eye drops. However, in many cases, lack of continuous release of the drug and issues with patients using the droppers properly reduces the effectiveness of the treatment. LayerBio is developing a biodegradable nanoparticle drug delivery system for an improved release of the drug over a minimum of four to six months per dose. The advantages of the company’s LayerForm technology include its ability to incorporate small molecules.
Dr Ken Mandell, LayerBio’s Founder and CEO, said: “It is critical that we develop long-acting alternatives to eye drops that provide around-the-clock coverage for patients suffering for glaucoma. The ability to offer continuous coverage and guaranteed compliance is vital to preventing progression of disease.” Nanotechnology has helped the team‘s work take great strides forward and the same is true of cancer treatments. Also in the US, scientists are working on ‘nano-cocoons’, an idea being developed by a team at North Carolina State University and the University of North Carolina, where the co-authors on the research project include PhD students Yue Lu, Margaret Reiff and Tianyue Jiang and Dr Ran Mo, a former postdoctoral biomedical engineering researcher.
Each bio-engineered cocoon consists of a single DNA strand in the shape of a ball of yarn, which is 150 nanometers wide and which can carry large amounts of anti-cancer drugs to release into cancer cells. The team says that the surface of the cocoon carries folic acid molecules known as ligands that bind to cancer cells and force them to suck in the nano-cocoon. Also, the nano-cocoons are less toxic than other systems which use synthetic materials and are easier to manufacture because of their self-assembly nature. Dr Zhen Gu, senior author of a paper on the work and an assistant professor in the joint biomedical engineering program at NC State and UNC Chapel Hill, said: “We’re very excited about this system and think it holds promise for delivering a variety of drugs targeting cancer and other diseases.”
Figure 2: A key advantage of the DNA brick method is its modularity, which allows for a variety of prescribed crystal shapes to be designed and constructed. Credit: Wyss Institute at Harvard University
