The long-term future envisioned by nanomedicine researchers includes incredibly tiny therapeutic agents that smartly navigate under their own power to a specific target—and only that target—anywhere in the body. On arrival, these self-guided machines may act in any number of ways—from delivering a medicinal payload to providing real-time updates on the status of their disease-fighting progress. Then, having achieved their mission, they will safely biodegrade, leaving little or no trace behind. These so-called nanobots will be made of biocompatible materials, magnetic metals or even filaments of DNA: all materials carefully chosen for their useful properties at the atomic scale, as well as their ability to slip past the body's defenses undisturbed and without triggering any cellular damage.
Although this vision will likely take a decade or two to fulfill, medical researchers have already begun addressing some of the technical problems. One of the biggest challenges is making sure the nanodevices get to their target in the body.
Most drugs on the market today readily float through the body in the bloodstream, either after being injected directly into the blood or, in the case of pills, getting absorbed into the bloodstream from the gastrointestinal tract. But they wind up traveling both to where they are needed and to where they can cause unwanted complications. Sophisticated nanomedicines, in contrast, are being designed to be guided to a tumor or other problem site, where their medicinal payload is released, reducing the chance of side effects.
Magnetic fields and ultrasound waves are the leading candidates for guiding nanomedicines in the near term, says Joseph Wang, chair of nanoengineering and a distinguished professor at the University of California, San Diego. In the magnetic approach, researchers embed nanoparticles of iron oxide or nickel, for example, within a particular medication. They then use an array of permanent magnets positioned outside a mouse or other subject and push or pull the metallic medicine through the body to a selected site by manipulating various magnetic fields. In the ultrasound approach, researchers have directed sound waves at medicine-containing nanobubbles—causing them to burst with enough force that the bubble's cargo can penetrate deep within a targeted tissue or tumor.
Last year medical researchers at Keele University and the University of Nottingham, both in England, added a helpful twist to their magnetic approach in work aimed at healing broken bones. They attached iron oxide nanoparticles to individual stem cells and then injected the preparation into two different experimental environments: fetal chicken femurs and a synthetic bone scaffold made from tissue-engineered collagen hydrogels. Once the stem cells arrived at the break, the researchers used an oscillating external magnetic field to rapidly shift the mechanical stress on the nanoparticles, which in turn transferred the force to the stem cells. This kind of biomechanical stress helped the stem cells to differentiate more effectively into bone. New bone growth occurred in both cases—although overall healing was uneven. Eventually the researchers hope that adding various growth factors to the iron oxide–studded stem cells will make the repair process smoother, says James Henstock, a postdoctoral research associate at Keele's Institute for Science and Technology in Medicine.
The primary drawbacks to the magnetic and acoustic approaches are the need for external guidance—which is cumbersome—and the fact that magnetic fields and ultrasound waves can penetrate only so far into the body. Developing autonomous “micro motors” for the delivery of therapeutic cargo could surmount those problems.
Such micro motors would rely on chemical reactions for propulsion, but toxicity is an issue. For example, oxidizing glucose, a sugar molecule found in the blood, would generate hydrogen peroxide, which could be used as a fuel. But researchers already know that this particular approach would not work in the long run. Hydrogen peroxide corrodes living tissue, and glucose in the body would not produce enough hydrogen peroxide to adequately power micro motors. More promising are efforts to use other naturally occurring substances, such as stomach acid (for applications in the stomach) or water (which is abundant in blood and tissues), as power sources.
Accurate navigation by these self-propelling devices may be an even greater hurdle, however. Just because nanoparticles can move anywhere does not mean that they will necessarily travel exactly where researchers want them to go. Autonomous steering is not yet an option, but a work-around would be to make sure that nanomedicines become active only when they find themselves in the right environment.
To accomplish this trick, researchers have begun creating nanomachines out of synthetic forms of DNA. By ordering the subunits of the molecule so that their electrostatic charges force it to fold in a particular configuration, scientists can engineer the constructs to perform various tasks. For example, some DNA segments may fold themselves into containers that will open and release their contents only when the package comes across a protein important to a disease process or encounters the acidic conditions inside a tumor, says University of Chicago chemistry professor Yamuna Krishnan.
Krishnan and her colleagues envision more advanced, modular entities made of DNA that could be programmed for different tasks, such as imaging or even assembling other nanobots. Yet synthetic DNA is expensive—costing about 100 times more than more traditional materials used to deliver drugs. For now, then, the price discourages drug companies from investing in it as a candidate for treatments, Krishnan says.
All of this may be a far cry from building a fleet of smart submarines reminiscent of Proteus in the 1966 film Fantastic Voyage. Still, nanobots are finally moving in that direction.