Nanotechnology primer

Nanotechnology. What does it mean to you? How does it affect health? Does the phrase only conjure up images of Crichton-esque nanobots with a sinister motive?

Nanotechnology is a field defined solely by its size. By definition, it involves the manufacture and manipulation of materials at the atomic or molecular level--materials which are typically less than 100 nanometers in diameter. (For comparison, a human hair is roughly 50,000 nm thick, and a piece of paper 100,000 nm thick).

This technology has potential applications in a host of fields. For example, it's been used as a windshield defogger. They can be used for stain repellents, and even as artificial bone. Really, the sky's the limit right now as far as applications go, but you can find those in current use via this catalog of products.

Since I'm writing about it here, you may have guessed that those applications include a wide range of health technologies. While many of these have the potential to significantly benefit human health, a recent recall in Germany shows that they also have the potential to be a detriment, rather than a boon, to health.

Federal regulators said Thursday they want to get a better handle on the burgeoning use of nanotechnology in everyday products, as their German counterparts struggle to understand why nearly 100 people suffered respiratory problems after using a novel cleaning product made with the submicroscopic particles.

Still, the NIH has invested millions in nanomedicine: the application of nanotechnology to medicine.

This knowledge will lead to the development of new tools that will work at the "nano" scale and allow scientists to build synthetic biological devices, such as tiny sensors to scan for the presence of infectious agents or metabolic imbalances that could spell trouble for the body, and miniature devices to destroy the infectious agents or fix the "broken" parts in the cells. This initiative is an important component of the NIH Roadmap endeavor because these tools will be developed and applied, not just for a single disease or particular type of cell, but for a wide range of tissues and diseases.

This kind of thing isn't 15 or 20 years away, either. Two papers just out this month already show some promise in applying nanotech to medicine.

The first, published here in PNAS, shows how a "nanosyringe" peptide can be used to directly deliver molecules inside of cells. They used a peptide (termed 'H [low] insertion peptide, or pHLIP) that inserts itself across a cell membrane at a low pH to move molecules--such as drugs--into the cell for release in the cytoplasm. Low pH is a key because normal cells are surrounded by an environment with a pH that's neutral to slightly basic (~7.4), while damaged sites and tumors are acidic, with a pH ~5.5-6.5. The authors demonstrate the insertion of their drug proxy, a fluorescent molecule that normally can't enter cells, in the figure at the left (where figure a is at a pH of 7.4 on the left panel, and at 6.5 on the right. The molecule is bound to actin in the bottom panel of cells).

The second, another PNAS publication, takes a similar approach, using a nanoparticle drug delivery system. However, instead of using a "nanosyringe" and injecting coupled molecules, the group used an old-fashioned syringe to inject nanoparticles mixed with a drug (docetaxel) and RNA aptamers directly into a tumor. In this combination, the nanoparticles form spheres, trapping the drug, while the RNA attaches to the surface of the spheres. It also recognizes an antigen on the surface of prostate cancer cells, acting like a molecular Velcro to localize the spheres to the cancer cells, which then internalize the particles. Once inside, the polymer gradually releases the drug and kills the cells.

Ideally, what may come out of this is a delivery system where these types of drug-delivering nanoparticles can simply be injected into the bloodstream, and seek out cancer cells (or other types of damage) within the body, while not affecting healthy organs.

Additionally, this technology has applications in infectious disease as well. For example, nanotechnology can be used to greatly increase the speed of pathogen identification. Edgar et al. (also writing in PNAS) have demonstrated a technique using a combination of bacteriophage and streptavidin-coated quantum dots (roughly one nanometer in size) that can be used to detect as few as 10 bacterial cells per milliliter in experimental samples (without having to grow them up or otherwise manipulate the cells, meaning it can be done very quickly). A limitation of the procedure currently is finding bacteriophage specific for the bacteria of interest. Additionally, this particular technique isn't useful for identifying viruses (since it relies on the bacteriophage to infect target bacteria in order to identify them), but other methods are in various stages of development that could rapidly detect a wider range of pathogens.

As you can infer from the number of PNAS links, this is a hot field with a lot of promise. And while the applications are potentially huge, the affect on the environment and human health need to be closely monitored to ensure that the technology is doing more good than harm. Still, definitely an area to watch in the coming years.

References

Reshetnyak et al. 2006. Translocation of molecules into cells by pH-dependent insertion of a transmembrane helix. PNAS. www.pnas.org/cgi/doi/10.1073/pnas.0601463103

Farokhzad et al. 2006. Targeted nanoparticle-aptamer bioconjugates for cancer chemotherapy in vivo. 103:6315-6320.

Edgar et al. 2006. High-sensitivity bacterial detection using biotin-tagged phage and quantum-dot nanocomplexes. PNAS. 103:4841-4845.

Image from http://www.sciencedaily.com/images/2006/04/060414005540.jpg