Tiny particles producing big hopes

UALR, UAMS scientists testing new method for killing cancer cells

BY CAROLYNE PARK

ARKANSAS DEMOCRAT-GAZETTE , p. 1 A, 5 A.

Little Rock scientists are developing a method for attacking cancer cells by injecting them with tiny magnetic particles that are then heated with low radiofrequency radiation, killing the cells from within.

Alexandru Biris, assistant professor and chief scientist at the University of Arkansas at Little Rock’s Nanotechnology Center, heads the research team that’s developing the technique in collaboration with the University of Arkansas for Medical Sciences.

“Once they’re heated, the cells disintegrate,” Biris said. “I’m very happy with some of the results that we’re getting.”

In early tests, the team killed about 98 percent of cervical cancer cells used in the study.

An article on their research was published last month in Nanotechnology, one of several scientific journals published by the Institute of Physics. The article is part of a growing body of research into ways nanotechnology can be used for medical treatments, said Carlo Montemagno, the journal’s North American regional editor.

There’s been a big increase in nanotechnology-based medical research in recent years, said Montemagno, also dean of the University of Cincinnati College of Engineering. Scientists believe such research will soon lead to major medical advances.

“Ultimately, nanotechnology will … have as profound an effect on the treatment of human health as the development of antibiotics and X-ray equipment,” Montemagno said.
Scientists are using nanotechnology to develop therapies that, because of their size, have the potential to minimize side effects and be “highly targeted and highly effective,” he said. They’re essentially engineering ways to combat diseases on the same minuscule scale at which diseases develop.

“Nanotechnology is unique in that the engineered structures are of the same size scale as the fundamental molecules of life,” he said.

CANCER RESEARCH

In the past two decades, a number of nanotechnologybased products have been developed for the treatment of a variety of diseases and disorders, including influenza, multiple sclerosis, breast cancer and fungal infections.

The technique being developed in Arkansas involves injecting cancer cells with highly magnetic cobalt particles surrounded by layers of graphitic carbon. The particles — called nanoparticles — are about 7 nanometers in diameter. That’s a few thousand times smaller than the diameter of a human hair, Biris said.

A nanometer is one-billionth of a meter.

Through a high-powered microscope, the nanoparticles look like tiny black clouds clustering in and around the cancer cells, penetrating even into the nucleus. Once inside the cells, they’re heated with a low radiofrequency radiation, like that used in some electronic or electromagnetic devices.

The heat obliterates the cell, killing it completely, Biris said.

Dr. Piotr Grodzinski, director of the National Cancer Institute’s Alliance for Nanotechnology in Cancer, said the concept isn’t new. Scientists have experimented for years with injecting tumor cells with different types of nanoparticles and then heating them with lasers or radiofrequency radiation.

What is new is the type of nanoparticles developed by Biris’ team.

Other researchers have experimented with different materials, such as gold and carbon.

“The whole area is really advancing, with lots of innovations,” said J. Donald Payne, president and chief executive officer of Nanospectra Biosciences Inc.

The Houston-based company started clinical trials this year to treat patients with head and neck cancer using materials developed at Rice University. Its method uses nanoparticles made of a gold shell and silica, or glass, core heated with near-infrared light.

Payne declined to comment on the status or results of clinical trials, other than to say they had to prove the methods’ safety and effectiveness before they could earn FDA approval to test it on humans.

Another example is from Dr. Steven Curley, a professor at the University of Texas M.D. Anderson Cancer Center, whose team of scientists from different institutions has had success killing liver-cancer cells using carbon nanotubes heated with radio waves.

Vladimir Zharov, professor and director of the Phillips Classic Laser Laboratories in the UAMS Winthrop P. Rockefeller Cancer Institute, did research using gold nanoparticles heated by laser years before working with Biris on the carbon-coated cobalt particles.

MOVING TO CLINICAL TRIALS

The Arkansas team is at least two years away from doing clinical trials on humans, Zharov said.

“We need to test lots of issues,” he said.

Ongoing research is focusing on how the technique affects surrounding tissues and how to get the nanoparticles to the cancer cells. The nanoparticles’ graphitic carbon outer layers are expected to reduce toxicity of the cobalt core and minimize side effects, he said.

The team is working on bonding the nanoparticles to antibodies that will essentially pull them through the bloodstream directly to cancer cells.

By targeting all cancer cells in the bloodstream, rather than just tumors, hopes are the technique would prevent spread of the disease to other parts of the body and reduce cancer recurrence, Biris said.

“If all the cells are killed, they’re not going to be able to regenerate,” he said.

Grodzinski, with the Alliance for Nanotechnology in Cancer, said it can take a long time for scientists to get to the stage where they can experiment on people.
First scientists have to determine whether the nanoparticle is safe for use inside the body, how to get it to go to the tumor or cancer cells, and whether it can be heated without harming nearby healthy tissues.

The National Cancer Institute started the alliance three years ago in hopes of propelling such research forward. It was the first time the institute — which traditionally funds biology and clinical research — agreed to fund a technology-based program for the purpose of advancing cancer treatment, he said.

The alliance has brought together oncologists, biologists, engineers and physicists who have produced a large amount of research in a short period of time, Grodzinski said. It has about a dozen clinical trials under way.

While no Arkansas institutions are part of the alliance, the UALR and UAMS team’s research is a “promising study which allows to treat tumors locally while not using chemotherapic drugs,” Grodzinski said.

“I think we can all be cautiously optimistic that some of these things will actually produce very significant solutions…. It’s a slow, tedious process. Nevertheless, it will definitely pay off.”

Outside of UALR and UAMS, the 12-person research team also includes Steve Trigwell, a senior research scientist with NASA’s Electrostatic and Surface Physics Laboratory at Kennedy Space Center; Dorin Boldor, an assistant professor with the AgCenter at Louisiana State University; and Alexandru R. Biris and Dan Lupu of the National Institute for Research & Development of Isotopic and Molecular Technologies in Romania. Alexandru R. Biris is the father of Biris at UALR.

Arkansas Democrat-Gazette/BENJAMIN KRAIN
Dr. Alexandru Biris (left), chief scientist of the UALR Nanotechnology Center, and a team of doctoral students, Enkeleda Dervishi, Meena Mahmood and Jerry Li, have developed nanoparticles that can be injected into cancer cells and heated with radio-frequency radiation to destroy the cells from within.

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