NEWS

Nanotechnology Getting Off the Ground in Cancer Research

Judith Randal

Researchers at New York’s Memorial Sloan-Kettering Cancer Center have created a novel means to administer radiation therapy by, in effect, cobbling together some off-the-shelf items. Although the only patients on the receiving end of their "nanogenerator" so far have been mice fitted with human cancers (prostate and disseminated lymphoma), the results were the stuff of which oncologists’ dreams are made.

Injections of single atoms of actinium-225 (an alpha-particle emitter) that were individually caged in specially constructed molecules supplied the treatment’s radioactivity. Those molecules were coupled to monoclonal antibodies targeted at the interior of tumor cells. The research team, led by Michael McDevitt, Ph.D., wrote in the Nov. 16 issue of Science that just one single-dose injection "induced tumor regression and prolonged survival, without toxicity, in a substantial fraction of (the) animals." The researchers also reported that the novel technique was effective in cell cultures of six different types of malignancies.

Does all this smack of too good to be true? Perhaps. Cancer research has had its share of seeming "breakthroughs" that did not live up to expectations or that outright failed. Still, it could be that what matters more than whether the nanogenerator ultimately makes it into the clinic is that a broad pursuit of nanoscale science and technology may have a lot to offer oncology.

Just that possibility was front and center at an August workshop that was held in Gaithersburg, Md., by the National Institute of Standards and Technology (an agency of the Commerce Department) and the National Cancer Institute. The workshop focused not only on what is meant by "nano" but also on why this field—though clearly a very young one—may both enhance the understanding of cancer and contribute to mastery of it.

As for the term nano-, it comes from the ancient Greek for dwarf and in scientific parlance is a prefix signifying one-billionth part of any metric unit of measurement. The dimensions of molecules and their constituent atoms—of which all living and other matter is composed—are in the nanometer size range. Said George Whitesides, Ph.D., a Harvard University professor of chemistry who was the meeting’s keynote speaker, "most folks working in this field say it begins at 100 nanometers. By reference, this is 200 gold atoms across."



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Dr. George Whitesides (Credit: Jane Reed/Harvard News Service)

 
Since the 1947 invention of transistors and the subsequent invention of silicon chips on which to place them, computers have steadily become more powerful. The catch is that they are microelectronic systems, which means that they will be as powerful as it is possible to make them within a decade or so. The reason is that the transistors etched onto their chips can be made only a finite amount smaller that they are now, and that limit is rapidly being reached.

However, nanoscale transistors—i.e., transistors only a few atoms wide, rather than thousands of atoms wide as in microprocessors—would solve the problem by allowing as many as 10,000 times more to fit into the same amount of space. In fact, prototype nanoscale components that can be assembled into logic circuits, the building blocks of computers, already exist.

The market for nanocomputing will be so great, Whitesides maintained, that the information technology industry can be counted on to spend whatever it takes to make it happen. But, while he is sure that the cancer research community will use nanocomputers to crunch numbers and the like, he is less sure that the community will think of nanotechnology when it comes to exploring tumor biology itself. It is a question of sociology, he told the workshop: Whereas cancer research is traditionally hypothesis driven, nanotechnology is a "tool culture, and the two approaches are [philosophically] incompatible."

Whitesides, nonetheless, made a strong case for the nano approach to cancer research, saying that funders would be wise to set up programs and earmark money to nurture the development of the requisite tools. He added that the activities of nanoscale dimension structures within cells are so basic to carcinogenesis and other cancer-related events—metastasis and immune system changes, for example—that they cry out to be tracked on an atom-by-atom and molecule-by-molecule basis.

For example, scientists often work with batches of cells that, though they look the same, are really different because they are in various phases of their cycles and have been subjected to different environmental influences. Nanoscience, it is thought, will help cancer researchers make the needed distinctions.

It should also help to pin down how enzymes and other protein molecules—by being in constant motion and constantly changing shape—act both on each other and on cells, their components, and on the networks that some cells form. Similarly, there is a distinct possibility that nanotechniques will enhance the understanding of cell interfaces and of the pores on the cell that are their principal contact with the outside world.

Even more broadly there is this: Mitochondria and other subcellular structures—the chloroplasts of plants, for example—are as Whitesides put it, "incredibly sophisticated machines." So a major investment in getting an accurate picture of what makes them tick and how to emulate them could, he predicted, pay off handsomely. And, he added, it would be useful if the knowledge could be harnessed to repair broken subcellular structures or even to build them from scratch.

Then, too, nanotechnology, nanoscience, and nanoengineering are very much about building things that do not exist in nature. A picture of a square cell that was shown at the workshop served as an example, the point being that making cells in defined shapes and with defined neighbors can be expected, as Whitesides put it, "to make the cell a much more tractable object for detailed study than it has been in the past."

So what tools will this emerging field need? Thanks to the 1986 invention of the scanning tunneling electron microscope and later elaborations of it, scientists can see for themselves how certain atoms in certain molecules behave.

In addition, so-called quantum dots are poised to come into their own. Quantum dots are semiconductor crystals a few nanometers across that can be used instead of fluorescent dyes to tag molecules and their component atoms. The particles are much less prone to fade and bleed than the dyes, and varying their size causes them to display different colors when exposed to a single light source. With conventional fluorescent tagging, by contrast, a different source of light is needed for each color to be visible.

GoThere are other developments on the horizon that exploit nanoparticles. Ordinarily, for example, small samples of DNA have to be "amplified" (i.e., enlarged) by polymerase chain reaction (PCR) before they can be characterized. But by marrying tiny bits of DNA to gold nanoparticles, two Northwestern University chemists—Chad Mirkin, Ph.D., and Robert Letsinger, Ph.D.—have devised a system that, in many cases, does the job without that preparatory step. "Our system is just as sensitive as the PCR system," said Mirkin, "and a whole lot simpler."



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Using a laser method, Josef Kas, Ph.D., and colleagues at the University of Texas at Austin have developed an "optical stretcher" that can classify cells based on the elasticity of their cytoskeletons. Above are optical stretching images of a red blood cell.

 
And then there are nanoshells: nanometers-wide beads that have a silicon core and an outer metal wall. At Rice University in Houston, Naomi Halas, Ph.D., and her colleagues have found that the beads can be made to absorb or scatter specific wavelengths of light by adjusting the ratio between the diameter of their cores and the thickness of their outer walls. They can thus be tailor-made for a variety of analytic and diagnostic purposes and very likely will have other biomedical applications.

Nor does that exhaust the possibilities of applications of nanotechnology. Take screening for cervical cancer with Pap smears, which became routine shortly after World War II. While the screening has, conservatively, saved hundreds of thousands of lives, it still produces findings that make it difficult to tell which smears are genuinely suspicious and which are not.

Now Josef Kas, Ph.D., a physicist at the University of Texas at Austin, has tackled the problem with a laser method he invented that tests cells for elasticity. The work strongly suggests that if the cells that Pap smears capture really are premalignant, they will stretch far more than their innocuous counterparts. Why? Because one of the early events of cancer onset is the collapse of the nanoscale inner support—the cytoskeleton—of the affected cells. Kas’s colleagues at Houston’s M. D. Anderson Cancer Center will soon test the concept further, he said.



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Dr. Josef Kas

 



             
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