a large number of them can be inserted without interfering significantly with cellular functions.

A key feature of PEBBLE structures is that they can be engineered to fluoresce in the presence of various small molecules or ions, such as oxygen, nitric oxide, calcium, potassium, and zinc, among many others. By flooding a cell with the PEBBLE nanosensors and then monitoring the cell under a microscope, investigators can observe the distribution of oxygen, nitric oxide, or other target molecules throughout the cell and monitor its evolution in time. With a little cleverness combined with a thorough knowledge of physics, chemistry, and cellular biology, it is possible to measure a great number of cellular metabolic activities, including changes in temperature, viscosity, and local magnetic and electric fields. “The beauty of this,” Philbert said, “is that we can now begin to add richness to the data sets in local areas in the cell where there may be intracellular electrophoresis contributing to the association of proteins, many of which have very large electrical dipoles.”

Another area of research pursued by the Philbert laboratory is the incorporation of Photofrin (porfimer sodium), a light-activated cancer drug, into nanostructures. Normally, Photofrin cannot cross the blood-brain barrier and thus cannot be used to treat brain cancer by conventional means. Because of the size of nanostructures, however, when the drug is incorporated into them it can cross the blood-brain barrier and target the tumor cells. A laser device is then used to activate the Photofrin and destroy the tumor cells. In experiments with rodent models, the treatment has dramatically increased survival rates. Without treatment, the brain tumors kill 100 percent of mice within 10 to 12 days. With treatment, about 60 percent of the mice are still alive after 39 days and about 40 percent are alive after 3 months.

Nanostructures are not expensive to make, costing about a dollar a kilogram for the materials incorporated into the most common ones. Synthesis demands a great deal of expertise, however, and the high cost is acquired through the requisite toxicology screening and federal approval processes. “Still,” stated Philbert, “their potential to do so many things that cannot be done in any other way makes them well worth the investment.”



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