Long before gold nanorods, carbon nanotubes, and magnetic nanoparticles were first made in the lab, nanoscale structures made from biological materials were being, and continue to be, constructed in living organisms. Life wouldn’t exist without nanostructures. Proteins that help build our muscles, antibodies that fend off disease and infection, membranes that keep unwanted materials out of our cells, even the fundamental building block of life … DNA, all exist at the nanoscale. What makes nanotechnology for medical applications such a compelling field is the fact that biology already operates at the nanoscale. Why make a diagnostic tool or medical device the size of a cell phone when you can make one the size of a cell membrane?
Considering life naturally works on the nanoscale, much research is now underway to engineer nanostructures out of biological materials. Today I’ll discuss DNA.

DNA and Nanotechnology

Deoxyribonucleic acid, or DNA, is a relatively simple molecule structurally speaking. It is primarily made up of only four different building blocks - the DNA alphabet of the bases adenosine (A), guanine (G), thymine (T), and cytosine (C). The structure of DNA that people are most familiar with is the double helix where the bases A, G, T, and C form a twisted ladder. However, using these same four bases, one can construct almost any shape that is desired. The question, though, is … why build anything using DNA?

Why Use DNA to Build Nanostructures?

DNA is a robust and biologically compatible material that is relatively easy to put together. DNA can last for thousands of years, even has been extracted from fossils. It has been estimated that DNA has a half-life of over 500 years, meaning that after 500 years, half of the DNA in a sample remains intact. Using DNA synthesizer equipment, long strands of DNA can be readily assembled by sequentially attaching each base (A, G, T, C) forming a chain … like putting beads together on a string. Multiple copies of the synthesized DNA can then be cloned within living organisms, typically bacterial or yeast cells. In fact, many companies now exist that provide DNA synthesis as a service. For shorter strands of DNA and more complex molecular architectures, such as those used to create nanostructures, standard DNA amplification and replication techniques can be used. Most often, DNA nanostructures are made using widely-available polymerase chain reaction (PCR) machines or thermocyclers.

Types of Nanostructures from DNA

Some of the earliest structures made from DNA that were not used for genetic purposes were aptamers. Aptamers are sequences of nucleotides (DNA, RNA) or peptides that are constructed to have a high affinity for a desired target molecule. DNA aptamers have been made for targeting platelet-derived growth factor (PDGF) for treating age-related macular degeneration, for binding thrombin to maintain anticoagulation during heart bypass surgeries, and for attaching to nucleolin for treating acute myeloid leukemia (AML). Many aptamers are now undergoing clinical trials for a variety of therapeutic purposes.
While aptamers were first discovered in 1990, other, more complex DNA structures have been, and continue to be, developed. These include DNA origami and DNA nanotrains. In fact, DNA nanotechnology has been around since the 1980s with attempts to create non-biological applications of DNA such as computing. It are these architectures that most would consider being DNA nanostructures due to their complexity and multifunctionality.

DNA Origami, Nanotrains, and Cancer Nanomedicine

DNA Origami
Researchers have been able to construct all sorts of shapes using DNA … spheres, boxes, scissors. One area in nanomedicine where DNA origami and DNA nanotrains are showing potential is in drug delivery. By folding DNA into tubes or boxes that can be opened and closed, researchers have been able to load drugs into these nano-assemblies. The drug remains contained with the DNA vessel until the infected or diseased cells are reached. Once inside the cells, the DNA constructs break open and release the drug within its intended cellular targeted minimizing the potential for the drug to cause unwanted side effects and possibly reducing the amount of drug required. Feasibility studies have been performed on leukemia and lymphoma cells as well as breast cancer cells for delivery of doxorubicin.
Aside from DNA aptamers, several of which are in clinical trials, the clinical benefits of more complex DNA nanostructures are still to be proven. However, the versatility, biocompatibility, and robustness of DNA are features that could prove DNA to be a compelling alternative to non-biological nanomaterials such as metals and synthetic polymers. For more information on DNA origami see the downloadable PDF from Nature.
DNA origami
Click on image above to download PDF on DNA origami from the journal, Nature.
 


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