“Everything, when miniaturized to the sub-100-nanometer scale, has new properties, regardless of what it is,” says Chad Mirkin, professor of chemistry (and materials science, engineering, medicine, biomedical engineering and chemical and biological engineering) at Northwestern University. This is what makes nanoparticles the materials of the future. They have strange chemical and physical properties compared to their larger-particle kin. The thing that matters about nanoparticles is their scale.
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Nanoscale materials are used in everything from sunscreen to chemical catalysts to antibacterial agents–from the mundane to the lifesaving. “I spilled wine at a Christmas party once, and I was terrified. Red wine on a white carpet. And it wipes right up,” Mirkin recalled. “The reason is the nano-particulate used to coat the carpet keeps that material from absorbing into the carpet and staining the carpet.”
On a more sophisticated side, researchers are developing nanoscale assays used to screen for cancer, infection and even genes. Gold nanoparticles that have been doped with DNA can be used to detect bacteria in a person’s bloodstream, determining whether a patient has infection and what kind. Or they can be used to detect changes in a person’s immune system that reflect the presence of cancer. Nano-flares can measure the genetic content of cells, and light up–or flare–when they detect a specific cell of a doctor’s choosing, maybe cancer, stem cells or even the reaction to a small molecule used in a new drug.
So why do nanoscale things act this way? The scale allows for unique interactions among atoms and their constituent parts, and there are a few ways that this happens. For non-biological nanoparticles, it helps to think of a bowling ball, and where all its atoms are located. The vast majority are inside the ball, with a finite number at the surface, interacting with the air or the wooden lanes. Atoms inside the ball interact with atoms just like themselves, but atoms at the surface interact with ones very different than themselves, Mirkin explained. Now shrink that ball to molecular scales.
“The smaller you go, the ratio of surface to bulk atoms goes up,” he said. “At a larger scale, the atoms at the surface are relatively inconsequential. But at nanoscales, you could have a particle that is almost all surface. Those atoms begin to contribute very significantly to the overall properties of the material.”
These interactions play out in electronics, too, making material like graphene and quantum dots useful for tiny computers and communication devices. Nanoscale materials offer a smaller area for electrons to move around. And maybe most importantly for current research, on the nanoscale, you’re on the scale of biology.
Given all these uses and future promises, Mirkin said, most people generally embrace nanotechnology in everyday life, even though most don’t know what that actually means. Even controversial uses like sunscreen are pretty widely used, and often without knowledge of it.
“Much of it is going to be embedded in conventional products that we buy and don’t even think about,” Mirkin said. “There’s nothing inherently good or bad in terms of making things small. The issue ultimately is, what do they do, and what are they used for? Given the application, have we considered the proper safety analyses and implications? And so far, I think we’ve done a pretty good job.”
Nanoparticle-Filled Ink Conducts Electricity
Tiny bits of conductive metal are crucial components of modern electronics, but future generations may not need high-precision machines. Circuit boards could be drawn by hand, enabling paper electronics, disposable antennas and a wide range of other items. Researchers at the University of Illinois at Urbana-Champaign (and many other teams) are making conductive ink from silver nanoparticles, which they shrink using acid. The nanoparticles are suspended in a cellulose solution, so they have a greater viscosity and can flow from a pen, quite literally. A line drawing becomes a silver wire that can carry a current, enough to power an antenna or even a small LED display, like the light bulb at the top of the house in this lovely drawing. The pen allows circuits to be embedded on uneven surfaces–and it enables a new type of creative design.
Gold nanoparticles are used in a variety of new “sniffers” for cancer and other diseases. As cancerous cells grow, genes and proteins within cells change, and this process emits volatile organic compounds that can be detected–this is why some dogs can be trained to “smell” cancer. Nanoparticles can smell it, too, and in tiny concentrations. Israeli researchers a couple of years ago reported new gold nanoparticle sensors that can tell not only whether a person has cancer, but which kind–lung, breast, prostate or colon cancer. The benefit of such a system is its early-warning capability. Doctors could administer a simple breath test, and be able to tell whether a patient has the beginning stages of cancer–well before any tumors would show up on an X-ray or mammogram. And it’s not just cancer patients who can benefit. Chad Mirkin of Northwestern University is developing nanoparticles that can diagnose and treat disease, tracking cancer at earlier stages and even determining whether hospital patients have infections. If someone needs emergency surgery, it may not always be possible for doctors to obtain the person’s medical history, which leaves plenty of unanswered and potentially dangerous questions–does this person have diabetes? Is she at risk for blood clots? Nanoparticles can be used to answer these and other questions. Mirkin points to a relatively new test for sepsis, or blood infection, which has great promise for treating patients better and saving money. Sepsis can be fatal if not treated quickly and thoroughly, but tests to determine a person’s infection level can take three days to complete–meanwhile, the patient is pumped full of antibiotics. But gold nanoparticles functionalized with DNA can identify whether or not someone has sepsis, and which bug is running rampant through his bloodstream, Mirkin said. “It’s the difference between a $20 test and hundreds of thousands of dollars in antibiotics,” he said.
Perhaps no other product demonstrates more clearly the strange behavior at nanoscales than something called Osorb. An accident of chemistry, the swellable glass material was intended to react with trace molecules of explosives, which would have made it a valuable security tool at places like airports. But something very weird happened in the development process, recalled Paul Edmiston, Osorb’s designer and a chemistry professor at the College of Wooster in Wooster, Ohio. He and some graduate students were trying to design nanostructured silica–glass–to change colors in the presence of vapors. “We serendipitously discovered a formulation by which the nanoparticles we were assembling into this porous glass film had become flexible. Instead of being a solid, they had the ability to swell,” he said. “Yeah, we had the color change, but it soaked up the entire volume of the test solution. We put more on and it sucked up more. It just expanded.” (Watch a video of that here). Edmiston was intrigued, but shelved the product in search of something that would satisfy the need for explosives detection, which was the point of his research grant. “It was like, ‘Well, that’s not going to work on a boarding pass,'” he recalled with a laugh. A graduate student resurrected it later and the team realized the material had some very interesting properties–especially its complete lack of reaction to water. Molecules can pass through the empty space between the nanosize silica, but water doesn’t, Edmiston said. This makes it extremely useful for water cleanup. The swellable glass, now named Osorb and marketed commercially by a spinoff called ABS Materials, can soak up oil and other organic material, and you can wring it out afterward and use it again. How does glass swell? “Chemically, it’s halfway between the window pane glass in your house, and the caulk that’s around your sink,” Edmiston explained. “Those type of ingredients, from a chemical level, build them up into a architecture that has the ability to expand and contract.” Osorb is already being used in places like parking lots, where it can absorb oil from leaky cars and prevent it from washing into bodies of water. It can be decorated with other material, like iron, to capture chemicals like phosphate. Edmiston has a new grant to study how this works, because he’s not sure if there’s a biological factor at play. One other weird thing: As it swells, it generates a remarkable amount of force, Edmiston said. It can lift 60,000 times its own weight. “If you had a coffee can of it, that’s enough to lift a car,” he said. “You might imagine we discovered that the hard way. We’ve broken a number of things in the lab because you just cannot contain it.”
Fighting Cancer At The Source
If cancer does take hold, nanoparticles can help with this, too. The dog in this CT scanner is a prostate cancer patient, undergoing a clinical trial to determine the safety of radioactive gold nanoparticles to treat his disease. Dogs develop an aggressive form prostate cancer much like human men, and a recent study at the University of Missouri could eventually lead to targeted treatment for the human form of the disease. Sandra Axiak-Bechtel, an assistant professor of oncology at the MU College of Veterinary Medicine, said the study’s main goals were to determine whether the gold nanoparticles were safe–and they were. Dogs showed no swelling, toxicity or changes in their livers, kidneys or bone marrow. The dogs underwent CT scans to determine the sizes of their tumors, and then radiologists injected them with a purple liquid containing radioactive gold nanoparticles. The particles were rendered radioactive in MU’s Research Reactor, Axiak-Bechtel said in an interview. Targeting tumors with radioactive particles is not a new concept, but the gold nanoparticles are. Earlier research showed it could be effective in mice, so the team wanted to try it on dogs, too. “A lot of owners that come in are very excited about something new that might be more effective than what we have to offer, and the potential to help men in the future–most people are very excited about that,” Axiak-Bechtel said. Again, nanoparticle treatments can work for diseases beyond just cancer, including bacteria and viruses. At IBM, researchers in California have built degradable nanoparticles that can glom onto drug-resistant bacterial strains and rip them open, draining their contents. The polymer particles break apart when they finish killing bacteria, and flush away with the invaders they destroyed. This is possible because of the particles’ size, which nicely attaches to the exterior wall of a bacterium.
Gene Therapy and Drug Delivery
Practically every week, scientists announce a new breakthrough in the ability of nanoparticles to deliver genes, drugs or chemical messengers inside cells. Nanoparticles of different shapes and chemical makeup can track down and target specific cells of a chemist’s choosing, and perform a variety of tasks. This image depicts DNA molecules (light green), packaged into nanoparticles by using a polymer with two different segments. One segment is positively charged, which binds the polymer to the DNA. This is shown in teal. The brown portion shows a protective coating on the nanoparticle’s surface. By adjusting the solvent surrounding these molecules, researchers at Johns Hopkins and Northwestern universities were able to control the shape of the nanoparticles. The team’s animal tests showed that a nanoparticle’s shape can dramatically affect how well it delivers gene therapy. This is possible because DNA behaves strangely among nanoscale particles, explained Chad Mirkin of Northwestern. Spherical nucleic acids, one of his lab’s inventions and an up-and-coming therapeutic technology, allow DNA to do something it otherwise can’t: Enter cells. To insert gene fragments into cells, researchers have to trick the cell, which is designed to block invasion. This is frequently done using viruses, but those can have a wide range of side effects. Instead, spherical nucleic acids attach short strands of DNA or RNA to a gold or silver nanoparticle’s surface, and the DNA molecules will organize into a spherical shape, Mirkin said. “You arrange a simple molecule in a spherical form, and it naturally enters cells better than anything known to man,” he said. “That is a paradigm shifter for how we think about creating new therapeutics–in this case, involving the world’s most important molecule, and learning how to arrange it in new forms on the nanoscale.”
Protective Coating For Your Skin
Cancer therapy and gene therapy are still largely lab-based uses for nanoparticles, with new papers publishing often, but few if any FDA approvals. That doesn’t mean the tiny particles aren’t ubiquitous, however–one prime example is something you use every day in the summer (or at least should). Sunscreen contains nanoparticles of titanium dioxide and zinc oxide, which are highly reflective and can prevent harmful solar radiation from penetrating your skin. This has been controversial for some time, however, with several environmental groups arguing for a moratorium on nanoparticle-containing sunscreens. But even sunscreens with micro-particles suspended in their lotion may contain nano-ones, inadvertently rendered nano by the manufacturing process. Previous studies have reached conflicting conclusions over whether nanoparticles can penetrate the skin. The debate continues to play out in the scientific literature, but a recent study at the University of Bath in the UK showed the titanium dioxide particles do not penetrate the top layer of skin, where they could theoretically do harm. “Using confocal microscopy has allowed us to unambiguously visualize and objectively assess what happens to nanoparticles on an uneven skin surface. Whereas earlier work has suggested that nanoparticles appear to penetrate the skin, our results indicate that they may in fact have simply been deposited into a deep crease within the skin sample,” said professor Richard Guy from the university’s Department of Pharmacy & Pharmacology, in a press release. Nano-coatings can protect more than your skin–they can make paper waterproof, protect carpets and clothing from stains, and even actively repel dirt from surfaces.
Nanomaterials In The Food Supply
The most controversial and arguably least well understood impact of nanotechnology is its impact on our food supply. Nanoparticles could be used as a pesticide or as a fertilizer, but some research shows they could damage crops and can even be fatal. Zinc oxide–that sunscreen ingredient, also found in tons of cosmetics and electronic devices–can accumulate in plant tissues, according to a study of soybeans published in August by _ Proceedings of the National Academy of Sciences_. Plant roots and root nodules can take up and store high concentrations of nanoparticles, and at high exposure levels, the plants were unable to fix nitrogen, Science Now reported at the time. “Is this an indication we should be worried about the food supply? I don’t know,” study author Patricia Holden told Science Now. “It’s important that the scientific community asks these questions in advance.” To that end, the federal Agricultural Research Service, part of the U.S. Department of Agriculture, is in the middle of a three-year study investigating the use of silver nanoparticles for pest control. While some studies have addressed toxicity of nanoparticles in aquatic environments, there’s very little research on the impact of silver nanoparticles on terrestrial creatures, the ARS points out. Much more work still needs to be done.