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Prostate cancer cells with fluorescently labeled cancer cells (red). Photo Courtesy MIT Press Office and Benjamin A. Teply

Prostate cancer cells with fluorescently labeled cancer cells (red). Photo Courtesy MIT Press Office and Benjamin A. Teply

11/14/2006

Tiny Particles Target Big Diseases

By:  Patrick Barry

Imagine swarms of millions of microscopic "agents" -- hundreds of times smaller than a red blood cell -- coursing through your blood to keep you healthy.  Like little robots, they would be custom-programmed to latch on to diseased cells and then, perhaps, signal the doctor by glowing a colored light, or maybe enter the cells and repair them, or both.

Sound like science fiction?  Only a few years ago, most scientists thought so too.  But that has changed.  Research on these microscopic agents, known as nanoparticles, has blossomed in recent years.  Much of this "sci fi" technology now exists in the lab, and the most advanced projects are even beginning clinical trials.  Once-skeptical scientists now talk excitedly about the potential of these nanoparticles, and the technology appears poised to become a powerful new tool for diagnosing and treating disease.
"It's growing very rapidly," said James Leary, a professor of biomedical engineering at Purdue University.  Leary has been working on nanoparticles since the field emerged roughly 10 to 15 years ago.

"[Five] years ago, this was kind of a renegade bit of science.  It's come a long way in terms of people accepting that this is probably a wave of the future in terms of drug-delivery systems," Leary said.

In traditional medicine, a doctor has virtually no control over what becomes of a drug after it enters the body.  Usually, the drug simply dissolves into the bloodstream and goes wherever the current takes it, affecting whatever organs and tissues it happens to encounter.  That's why some drugs have side-effects, and why the harsh chemicals used to attack tumors in chemotherapy ravage the patient's whole body.

Nanoparticles offer more control.  Scientists design tiny vessels to carry the drug inside the body.  These vessels are vanishingly small: larger than a typical molecule but smaller than a virus.  Millions of them could fit inside of a single cell, making them the right size to easily enter cells, yet not so small that the kidneys would quickly filter them out.  Each would only carry a miniscule dose -- perhaps only a few molecules of the drug -- but billions of them could easily be given in a single injection.

To ensure that these vessels deliver the drug only to the right cells (the sick ones), scientists attach special "address" molecules to the nanoparticles.  When the cells of your body become sick, they often display uniquely shaped molecules on their outer surfaces as a way of telling your body, "hey, I'm sick over here."  By choosing an "address" molecule that exactly fits this unique shape, like a key fitting a lock, the scientists assure that the nanoparticles will only attach to the sick cells.  Thus, no side-effects.

Once it attaches to the target cell -- a tumor cell, perhaps -- the nanoparticle enters the cell and releases its medicine.

As the field has grown, though, the number of uses that scientists have dreamed up for nanoparticles has grown as well.  Some kinds of nanoparticles, called "quantum dots", can be engineered to glow a certain color when they contact a cell with a certain disease, allowing extremely sensitive diagnoses.  Currently this is only done with cells removed from the body or in animals, but if these quantum dots prove safe, doctors may eventually use them inside the body as well.

Other nanoparticles can be injected into the body to enhance the contrast in MRI images, making a specific organ or feature stand out.  Still others can do complex, multi-step tasks.  For example, they might linger harmlessly in the bloodstream until a certain problem arises, then find and enter the problem cells, anchoring themselves at a certain place within those cells while they churn out copies of a gene to remedy the problem.

The "palette" of materials for making nanoparticles has also grown.  Today, some nanoparticles are made from fats, others from RNA, still others from polymers, semiconductors, or bio-nanotubes (tube-shaped bundles of proteins).  Some are even made of gold.

The real boost in momentum for nanoparticle research, according to Leary, came when the National Institutes of Health began funding nanoparticle research in earnest.

"We have been funding more and more of this type of research within the last [four or five] years," said Catherine Lewis at NIH's Division of Cell Biology and Biophysics.  "And I do think that the interest in this [at NIH] is increasing a lot."

Not surprisingly, some of this research is further along than others.  Bio-nanotubes, for example, are still mostly a laboratory curiosity, according to Uri Raviv, a post-doctoral researcher at the University of California, Santa Barbara.  Raviv and his colleagues have produced bio-nanotubes in the lab, and he believes that they have potential for use as medical nanoparticles.  But only after several more years of work could they consider testing them in humans, Raviv said.

In contrast, nanoparticles made from fat-like molecules are beginning phase-one clinical trials.  A group of researchers at Georgetown University Medical Center have developed a kind of nanoparticle that can deliver a cancer-fighting gene (p53) to tumor cells.  The trials will be on 20 patients with solid thyroid tumors, including patients whose tumors have spread, or "metastasized", to other parts of their bodies.

"We are not targeting only the thyroid tumor, but we are also targeting specifically the metastatic tumor," said Esther Chang, the group's leader.  "That makes us very different."  In experiments on mice, their nanoparticles succeeded in killing both the normal and metastatic tumors, she said.

Hurdles do remain for nanoparticle research, however.  A successful design will eventually need to be mass produced.  Billions of these little "agents" could be inside a single drop of water -- how do you check for defects?  Malformed particles could behave erratically in the body, but quality control won't be easy.  There's also a question of what becomes of these materials after they are broken down by the body and excreted in the urine.  Are there any downstream environmental problems to worry about?

Despite the progress that's been made, nanoparticles remain a relatively new and radical notion in medical science.  But now that they're out of the starting gate, this should be a very interesting race to watch.

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