Targeting Cancer Cells with Nanoparticles
Cancer is the number two cause of death in the United States, killing over 550,000 people annually according to the American Cancer Society’s 2009 Cancer Statistics report. Although there has been significant progress in the treatment of cancer over the past 20 years, the overall five-year survival rate is still only 66%. Some of the causes for this high mortality rate include tumor identification and classification, late diagnosis, and incomplete or inadequate treatment – all of which lead to poor patient outcomes.
The majority of promising new cancer therapies target selected cancer-activated biochemical pathways. To maximize the clinical utility of these new therapies, researchers must identify and understand the molecular characteristics of each patient’s tumor, and to obtain as much diagnostic and prognostic information as possible for each patient.
Enter nanomedicine. Led by Elena Rozhkova, scientists from the U.S. Department of Energy’s (DOE) Argonne National Laboratory and the University of Chicago’s Brain Tumor Center have developed the first nanoparticles that seek out and destroy glioblastoma multiforme (GBM) brain cancer cells without damaging nearby healthy cells.
Nanomedicine, an offshoot of nanotechnology, refers to highly specific medical intervention at the molecular scale for curing disease or repairing damaged tissues, such as bone, muscle, nerve, or brain cells. Nanoparticles – anywhere from 100 to 2500 nanometers in size – are at the same scale as the biological molecules and structures inside living cells. Cancer detection using nanoparticles shows great promise as a therapy for certain types of cancer. And the U.S. National Institute of Health (NIH) is taking nanoparticles very seriously. The NIH has established a national network of eight Nanomedicine Development Centers, which serve as the intellectual and technological core of the NIH Nanomedicine Roadmap Initiative.
Dr. Rozhkova’s solution involves chemically linking titanium dioxide nanoparticles to an antibody that recognizes and attaches to GMB cells, reports Science Daily. When they exposed cultured human GMB cells to these so-called "nanobio hybrids," the nanoparticles killed up to 80 percent of the brain cancer cells after 5 minutes of exposure to focused white light. The results suggest that these nanoparticles could become a promising part of brain cancer therapy, when used during surgery.
GMB is a particularly nasty form of cancer that often causes death within months of diagnosis. Titanium dioxide nanoparticles, a type of light-sensitive material widely used in sunscreens, cosmetics, and even wastewater treatment, can destroy some cancer cells when the chemical is exposed to ultraviolet light even without the use of antibodies. However – until now – researchers have had difficulty getting nanoparticles to target and enter cancer cells while avoiding healthy cells.
Titanium dioxide is not the only nanoparticle that shows promise in cancer therapy. Gold nanospheres – nearly perfectly spherical nanoparticles that range in size from 30 to 50 nanometers – are being used to search out and "cook" cancer cells. The cancer-destroying nanospheres show promise as a minimally invasive future treatment for malignant melanoma, the most serious form of skin cancer. Melanoma now causes more than 8,000 deaths annually in the United States alone and is on the increase globally.
The hollow gold nanospheres are equipped with a special peptide that draws the nanospheres directly to melanoma cells, while avoiding healthy skin cells. After collecting inside the cancer, the nanospheres heat up when exposed to near-infrared light, which penetrates deeply through the surface of the skin, explains study co-author Jin Zhang, Ph.D., a professor of chemistry and biochemistry at the University of California in Santa Cruz. This procedure is a variation of photothermal ablation, also known as photoablation therapy, a technique in which doctors use light to burn tumors. Since the technique can destroy healthy skin cells, doctors must carefully control the duration and intensity of treatment.
It’s basically like putting a cancer cell in hot water and boiling it to death.
"This technique is very promising and exciting," says Jin Zhang. "It’s basically like putting a cancer cell in hot water and boiling it to death. The more heat the metal nanospheres generate, the better."
Photoablation therapy can be greatly enhanced by applying a light absorbing material such as metal nanoparticles to the tumor. However, many materials show poor penetration into cancer cells and limited heat carrying-capacities. These materials include solid gold — as opposed to the hollow nanospheres used by Dr. Zhang and his colleagues. Other materials such as solid nanorods lack the desired combination of spherical shape and strong near-infrared light absorption required for effective photoablation therapy.
Dr. Zhang and his colleagues worked with the hollow gold nanospheres — each about 1/50,000th the width of a single human hair – to develop more effective cancer-burning materials. Previous studies by others suggest that hollow gold nanospheres (nanoshells) have the potential for strong near-infrared light absorption. However, until very recently, researchers have been largely unable to produce them successfully in the lab.
The following video shows how light-absorbing gold nanoparticles can also use epidermal growth factor receptors (EGFR) sites for cancer cell detection with simple white light:
NIH expresses the hope that nanomedicine — including the use of nanoparticles and eventually nanobots (see the h+ article "Nanobots in the Bloodstream" in Resources) – will allow scientists to build new devices for a wide range of biomedical applications. According to the NIH Roadmap, such technology would be used for “detecting infectious agents or metabolic imbalances with novel, tiny sensors, replacing ‘broken’ machinery inside cells with new nanoscale structures, or generating miniature devices that search for, and destroy, infectious agents.”
A second phase for the NIH nanomedicine program was recently approved. “Centers will continue to expand knowledge of the basic science of nanostructures in living cells, will gain the capability to engineer biological nanostructures, and then will apply the knowledge, tools, and devices to focus on specific target diseases,” reports the NIH Roadmap.
The idea is to apply “acquired fundamental knowledge” such as the experimental results obtained using titanium dioxide nanoparticles and hollow gold nanospheres to actually treat disease. Such targeted cancer therapies may ultimately ease the despair of millions of cancer victims worldwide.