Using parts of living cells in a smart nanotechnology-based system, researchers in Switzerland have demonstrated a “nanocarrier” that can target specific types of cells and light up in response to conditions in their immediate environment.
The work is part of a growing effort by scientists worldwide to develop nano devices that can circulate in the bloodstream, slip stealthily past the body’s immune system, attach to cancer or inflammatory cells (an important ability in diseases such as atherosclerosis and arthritis), and deliver a deadly drug payload–destroying some of the toughest diseases without the often debilitating side effects that can accompany chemotherapy (see “Nanomedicine”).
Already, early versions of such nano-based treatments have been approved for breast cancer. But Patrick Hunziker, a physician at University Hospital Basel, and Wolfgang Meier, professor of chemistry at the University of Basel, are attempting to trigger the release of the drugs at more precise locations and at release rates adjusted to have the most effect on a particular disease.
One promising approach to achieving this goal is to develop nanocarriers that can respond to cues in their immediate environment, similar to how living cells can open and shut membrane pores. Hunziker and Meier have just reported in the journal Nano Letters on a system that incorporates bacterial proteins that form such pores.
The researchers first developed a type of polymer that self-assembles to form hollow spheres about 200 nanometers across. During the assembly process, they introduce the pore proteins, which form channels in the polymer spheres. As in bacteria, where the pores can close to protect cells from acidic environments, these channels also open and close in response to changes in pH.
The researchers then demonstrated that the resulting nanocarrier could control the location and duration of a fluorescent signal–an ability that could be useful in lab diagnostics. To do this, they added another biological molecule to the mix, encapsulating within the spheres an enzyme that breaks down certain compounds, causing them to glow. They then added the nanocarriers to a solution containing these compounds.
In experiments in which the researchers add the enzymes directly to the solution, without using the nanocarriers, the compounds glow diffusely and for only a few minutes. When using nanocarriers, though, the light is concentrated within the spheres, where the enzymes are sequestered, and the signal lasts many times longer–about three hours. Combined with the ability (demonstrated in an earlier paper) to make the nanocarriers latch onto specific cells, the system could be used to highlight the location of these cells in lab tests.
Their current work also demonstrates the possibility of a switchable system that responds to local conditions. In the experiments, the spheres glowed only when the solution had the same acidity as structures called lysosomes located within cells. This is due in part to the pH sensitivity of the enzyme they used; but it is also, Hunziker says, because the pores are open at this level of acidity. This sensitivity could theoretically ensure that the fluorescent signal only switches on inside a cell.
The Swiss researchers are now testing the toxicity of the nanocarriers in animals and working on developing a system that could deliver an appropriate drug to targeted cells, perhaps by using synthetic channels, rather than the current bacterial proteins, which would open to deliver the drug once inside target cells.
Robert Langer, professor of chemical engineering at MIT, says the work is interesting, but also cautions that it is still at a very early stage–animal tests have yet to demonstrate its usefulness. Meanwhile, Theresa Allen, professor of pharmacology at the University of Alberta in Canada, is concerned that the use of bacterial proteins could trigger an immune reaction. But she also says the current nanocarrier system might be a useful diagnostic tool to analyze lab samples.
If the researchers are able to develop a working drug-delivery platform, they’ll still face stiff competition. Already-approved drug-delivery systems, for example, are now being modified to break down and release their cargo when they reach lysosomes.
But the new system demonstrates the ability to engineer a complex, smart nanocarrier, which could open the way for more powerful diagnostics and treatments.
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