Nanoparticles detect tumors earlier than any current imaging technology, study shows

National report - Specially designed nanoparticles may allow future dermatologists to noninvasively detect melanoma and other tumors that would otherwise be invisible, and to phenotype and stage early melanoma in the clinical setting, according to Washington University School of Medicine researchers.

Gregory Lanza, M.D., Ph.D., associate professor of medicine, and Samuel Wickline, M.D., professor of medicine at Washington University School of Medicine, St. Louis, have engineered nanoparticles to detect tumors using standard MRI equipment.

In a recent study, the researchers set out to use a normal-sized scanner to detect minute tumors by implanting human melanoma in immunoincompetent nude mice and injecting the mice with alpha(nu) beta(3)-targeted paramagnetic nanoparticles.

Specific targeting

Dr. Lanza and colleagues also demonstrated that the targeting of these particles to the angiogenesis was highly specific for that marker.

"In this case, it was alpha(nu) beta(3)-targeted paramagnetic nanoparticles. That is important because the amount of alpha(nu) beta(3) integrin and the degree of angiogenesis is correlated with the aggressiveness of the tumor," he says. "In essence, we demonstrated that we could target these particles and recognize angiogenesis produced by these very small tumors. We could detect it with a normal scanner, allowing us to characterize tumors' aggressiveness before resecting them."

Why nano?

Nanoparticles, in this case, are only 200 nanometers in diameter.

The small particle size actually increases the surface area per volume and increases surface payload, according to Dr. Lanza.

"When you do MRI imaging to detect molecular signature, using a homing molecule like an antibody, you would only be able to put on one or two gadolinium atoms. But when you use a particle, like a nanoparticle, you can put 100,000 gadolinium atoms on each particle," Dr. Lanza says.

Nanoparticles also provide increased circulatory half-life, so that when particles are injected in the blood they can circulate long enough to reach their target.

As effectively as they can carry imaging materials to highlight tumors, nanoparticles also can deliver cancer-fighting drugs to malignancies. And whereas an antibody might carry one molecule of a drug, a nanoparticle can carry 100,000 molecules to the target.

Future applications

Dr. Lanza predicts that it is only a matter of a couple of years - maybe less - before nanoparticles will play roles in detection and treatment of metastatic melanoma.

"I see that these nanoparticles, in the case of dermatology for melanoma, will be used to stage the primary tumor, in terms of its aggressiveness, detect metastases and ... even potentially provide localized treatment to these metastases to help to kill the tumor growth. That is our hope. That is our game plan," he says.

Preparing for human tests

Kereos, the company licensing these nanoparticles, is completing preclinical studies and manufacturing studies required to begin human clinical testing.

"When they start doing human clinical testing, they will be using these particles targeted to a wide variety of oncologic disease, including melanoma and probably including basal cell carcinoma," Dr. Lanza says.

The findings could help to change the current paradigm of medicine from one of reacting to one of more aggressively detecting and treating disease so early that patients do not suffer the diminished quality of life with treatment that they do today.

"You have to move the clock backwards if you want to make a difference in cancer," Dr. Lanza says. "You have to find it earlier and treat it when it is more susceptible - before a clinical event occurs. That is our whole paradigm."

The study was supported by the National Cancer Institute under the Unconventional Innovative Projects program. Philips Medical Systems provided major research support in terms of equipment and on-site clinical scientists.

Disclosure: Drs. Lanza and Wickline cofounded Kereos Inc., St. Louis, the company to which the nanotechnology they invented is licensed. The doctors are now minority stockholders in that company.