BioTechniquesVol. 41, No. 1 Tech NewsOpen AccessNanobiotechnologyLynne LedermanLynne LedermanSearch for more papers by this authorPublished Online:21 May 2018https://doi.org/10.2144/000112207AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinkedInRedditEmail Coming Into Its OwnTwo years ago, the first Technology News column citation reported that nanotechnology would probably continue to be best thought of as a collection of technologies capable of providing solutions to a wide range of biologic and mechanical problems, rather than as a distinct industry unto itself. It was also acknowledged that while it would be difficult to predict what the future held, nanotechnology should live up to its promise of facilitating research, leading to faster, cheaper nucleic acid sequencing and analysis, allowing development of hand-held detection and analytic devices, and increasingly take advantage of the capacity of biologic components to self-assemble. In this short period of time, nanotechnology has indeed become, if not an industry, then a field of its own within the biotechnology world. Having grown well beyond its origins in the semiconductor industry, the application of nanotechnology to biologic problems has matured enough not only to deserve its own name, nanobiotechnology, but to have spawned institutes devoted to its further development.Harnessing the ForceOne technology that is still laboring to escape the implications of its origin in the semiconductor industry is atomic force microscopy (AFM). AFM relies on a tiny probe to detect surface structure at the molecular level. According to Stuart Lindsay, Director, Center for Single Molecule Biophysics, Arizona State University, Tempe, AZ, AFM is “now at the horse and buggy stage, but should be a sleek racing car in a few years.” Although Lindsay and his group have a small NIH grant to use AFM for DNA sequencing, he acknowledges that this is “very blue sky research.” His group has made some progress, with a goal to make sequencing even faster and cheaper, but they have yet to prove this application. “The jury is still out on AFM making a contribution to DNA sequencing,” he says. One application where AFM is beginning to prove its worth is in quality control for the biotechnology and pharmaceutical industries. “AFM is not easy to perform, although it is easier than electron microscopy (EM),” Lindsay observes. In scanning EM, proteins can be identified using immunogold labeling. AFM recognition imaging can be done in situ in fluids, which is impossible for EM, which must be done in a vacuum. With AFM, chemical identification of individual proteins is also possible. Lindsay believes one of the most important applications will be in imaging biological signaling pathways through co-localization of factors and mapping of chemical composition of interacting factors, some of which may be in micromolar concentrations, others in nanomolar concentrations. Lindsay and colleagues have used AFM with antibodies to identify specific single molecules in a complex sample. Another important application of AFM is reading biologic and other parallel assays performed on nanometer scale arrays, allowing many more samples to be analyzed on tiny chips than would be the case if the arrays were spaced on a micrometer scale.Image 1. Three separate atomic force microscopy (AFM) images of preprogrammed patterns displayed on molecular lattices self-assembled from DNA cross-tiles. White bumps are individual molecules of streptavidin protein bound to biotin at specific points on the DNA lattice.Image courtesy of the Dwyer and LaBean groups at Duke University, Durham, NC.Thomas H. LaBean, Associate Research Professor, DNA NanoTech Group, Computer Science Department, Duke University, Durham, NC, is using DNA as an engineering material for nanofabrication and bimolecular computing applications. His group is studying self-assembling DNA nanostructures for formation of specifically patterned micron-scale objects with nanometer-scale feature resolution. Their latest work involves the creation of 80–90 nm fully addressable lattices with and without biotin labels as sites for writing patterns that can be imaged with AFM. LaBean speculates that biomedical applications of this technology will include the use of DNA lattices as molecular rafts to look at receptor clustering on cell surfaces to examine cell signaling pathways for such phenomena as apoptosis. This may allow separation of the consequences of receptor-ligand binding from the effects of receptor clustering in the absence of ligand binding.Nanotherapy“Nanotechnology is going hand-in-hand with biotechnology and medicine. It's a natural match,” says Lajos P. Balogh, Co-Director of the NanoBiotechnology Center, Roswell Park Cancer Institute, Buffalo, NY. Balogh and colleague Mohammed K. Khan, a radio-oncologist, are applying nanotechnology to targeting tumor microvasculature. The goal is to deliver radioactive gold nanoparticles to tumor microvasculature to irradiate the tumor locally, and reduce the systemic damage that external radiotherapy can cause. Balogh notes that most tumors can't grow without their microvasculature. A successful nanoagent will deliver both local radiation and an antiangiogenic therapeutic. There are many issues to solve, such as the biokinetics and bioaccumulation of nanoparticles, and specifically targeting particles to the tumor while avoiding accumulation in the liver and kidney and other areas where they are not needed or wanted. “I don't believe in passive targeting,” says Balogh. They are looking at using dendromers or spherical polymers and changing the surface charge, size, and flexibility as a means of more specific targeting.LaBean expects to see the use of nanoscale DNA lattices for drug delivery. An example would be to target the DNA raft to blood clots using single chain antibodies to cross-linked fibrin and other clot components, along with such “clot busters” as plasminogen activators, which would be released only near the clot.Thomas J. Webster, Associate Professor of Engineering, Brown University, Providence, RI, is looking at whether nanomaterials can serve as better growth supports than materials currently used for medical implants. The most effective materials will be those that support the growth of desired cells (e.g., neurons in the brain), while not inducing undesirable effects (e.g., formation of scar tissue). One area of interest for his group is the use of nanocoated metal for orthopedic implants, which is in preliminary stages. They hope to induce bone growth and infiltration into metal scaffolds without causing a foreign body reaction. Important applications will be for weight-bearing implants for hips, knees, and joints. Webster believes that even if coating particles are found to be toxic, they will be able to accomplish the same goal, perhaps by creating nanosurface features via lithography or anodization, rather than by coating with particles. Nanotechnology may help solve the high rate of postimplant surgical infection with normal flora via nanocoating of implants with antimicrobial particles (e.g., zinc or silver oxides), although this application, too, is in early stages.The Next GenerationIn May, Johns Hopkins University announced its new Institute for NanoBioTechnology. It became the latest in a movement to formalize the study and application of nanotechnology, which includes the Nanobiotechnology Center at Cornell, the NanoCenter at University of Maryland, the Nanocenter at the University of South Carolina, and others. Denis Wirtz, the associate director of the Hopkins venture, believes their effort will demystify the biomedical sciences for physical scientists and engineers, and the physical sciences and engineering for biologists. Peter Searson, the institute's director, agrees. “Each side will understand what the other is talking about.” The mission of the institute is to train a new generation of scientists and engineers in nanobiotechnology, where individuals will have a solid grounding in one field, and know enough about the other to collaborate effectively. Searson expects to see an understanding of how cells both function and malfunction at the molecular level to arise from this collaboration. The ultimate impact will be on diagnostics and therapeutics, new imaging techniques, and new treatment modalities. One clinical example they give is the treatment of cystic fibrosis. Searson speculates that this genetic disease might one day be treated by gene therapy involving the inhalation of synthetic nanoparticles carrying the cystic fibrosis transmembrane receptor gene, which is defective in patients with the disorder. A multidisciplinary team will be needed to solve the problems of creating particles that can carry the genetic material, cross the mucous membranes, and deliver the therapy effectively. Each step must be solved in a way that does not affect another.Image 2. Increased new bone formation surrounding orthopedic metal implants coated with nanoceramic particles. Greater amounts of bone growth were measured on tantalum coated with nanoparticles of hydroxyapatite when implanted into the calvaria of rats for 6 weeks compared with uncoated tantalum and tantalum coated with conventional hydroxyapatite.Image courtesy of Thomas Webster, Brown University, Providence, RI and Prof. Lee, Yonsei University, Seoul, South Korea.Bright Future“AFM is still far from a routine tool because it is not easy to operate,” says Lindsay. “The instruments are needlessly complicated, because AFM arose in the semiconductor industry for use in clean rooms and to be operated by robotics.” Lindsay expects AFM to continue to become more user-friendly in future. LaBean expects that applications of the DNA lattice technology will include further miniaturization of electronic circuits, memory devices, molecular photonics and robotics, and biosensors. He speculates that one day it may be possible to monitor mRNA in living cells and determine what genes are turned on and off. Balogh believes there is a “bright future in assays using nanoparticles for labeling” and in other applications.FiguresReferencesRelatedDetails Vol. 41, No. 1 Follow us on social media for the latest updates Metrics History Published online 21 May 2018 Published in print July 2006 Information© 2006 Author(s)PDF download