Won Park was hoping the result of the in vitro bladder cancer experiment using his nanoparticle technology wouldn’t just leave him seeing red.
Among the red-stained live bladder cancer cells was an area stained blue, which showed the nanoparticle therapy had killed the cancer cells. The experiment was a success.
Park, an associate professor of electrical, computer and energy engineering, together with collaborating researchers at the University of Colorado Cancer Center on the Anschutz Medical Campus, had developed a promising new type of bladder cancer therapy. Based on early-stage trials, this targeted nanotechnology-based approach to fighting cancer could be a breakthrough treatment.
“Delighted. Excited. Thrilled,” says Park, “but not surprised. We were expecting it. We demonstrated ablation of cancer cells.”
Park focuses his research on developing novel nanomaterials and nanostructures for photonic applications. In biomedical engineering, he develops complex nanomaterials that are used to detect and destroy cancer cells.
Bladder cancer is the fourth most common cancer among men in the United States, with more than 70,000 new cases annually. Researching targeted nanoparticles is a cutting-edge approach to treating bladder cancer, a disease that claims 14,000 deaths annually in the United States.
Bladder cancer therapies ranging from surgery to chemotherapy have remained basically the same since the 1970s, says Park, and include many side effects. One current therapy uses an attenuated form of a bacterium that causes tuberculosis, but despite the treatment the recurrence rate is about 40 percent.
Although Park has no formal bioengineering training, he is applying his broad engineering expertise to create new technologies and treatments.
In collaboration with Thomas Flaig, MD, a specialist in bladder cancer at the University of Colorado Anschutz Medical Campus, Park developed rod-shaped nanoparticles made of gold. The nanoparticles are designed to absorb light in the near infrared, a frequency that can penetrate the body up to a few centimeters.
The nanoparticles are coated with a protein that is the antibody to epidermal growth factor receptor, a protein present only on bladder cancer cell membranes. Normal urinary tract urothelium tissue does not express epidermal growth factor receptor, so the antibody coating - called Nano-aEGFR - ensures that Park’s nanorods only anchor onto the cancer cells.
An infrared laser beam is focused on the area where the nanoparticles are attached to cancer cells, causing the particles to absorb light and heat up. Cancer cells have a narrower temperature window for survival than normal cells. With this imaging-guided thermal ablation therapy, researchers heat the nanorods to a temperature that is lethal to them without harming normal cells. The nanorods are introduced into the bladder through a urinary catheter. When the treatment is finished, the nanoparticles are removed by draining the bladder. Park has also developed nanoparticles that, when added to the mix, fluoresce green under infrared light, allowing researchers to not only see the location of the cancer cells, but also to eradicate the disease in the same procedure. The fluorescent capability eliminates the need to use colored dyes.
The nanoparticles Park is working with are 20 nanometers in diameter and 40 nanometers in length and can only be seen with an electron microscope. To put that size into perspective, a sheet of paper is 100,000 nanometers thick.
The approach Park and his team of collaborators at the University of Colorado Cancer Center are using is nearly unparalleled in the arena of bladder cancer research. The collaborating researchers are one of few groups in the world conducting research using multifunctional nanoparticle therapy and the only team conducting animal studies. Results in mice have shown that the treatment works only when both nanoparticles and lasers are applied, indicating that the nanoparticle or laser alone is non-toxic and thus promising minimal side effects. A portion of the study has been accepted for publication in the Journal of Biomedical Nanotechnology. The remainder of the research will be published in the near future. “We have demonstrated the multifunctional use of nanoparticles,” says Park.
The next step will be to begin studies in larger animals and, if the technology continues to look as promising as it has so far, move onto human trials. Park and Flaig have formed a company called Aurora Oncology to develop the technology further so it can quickly move into the clinic. Once they perfect the nanoparticle technology for bladder cancer, they plan to begin work on oral and skin cancers. Since different cancers express different types of proteins, the protein antibodies added to the nanoparticles will need to change. Other than that, the technology remains the same.
“In the longer term,” says Park, “this technology can be applied to deep organ disease, like breast and prostate. Delivery into the body will be an issue that will have to be worked out. But for bladder and other accessible types of cancer, we can make an immediate impact.”