CORVALLIS, Ore. – An Oregon State University-led research team has successfully used nanotechnology to deliver diagnostic imaging agents to cancerous tumors. The specially designed “peptide” – or compound comprised of amino acids – attaches directly to cancer cells in animals by targeting the tumors’ low pH levels.
The breakthrough has immediate applications for detecting and defining tumors, researchers say. Even more importantly, this novel delivery mechanism has the potential to include delivery of other diagnostic and other therapeutic agents that can be targeted directly to growing cancers.
Results of the research will be published in the December issue of the journal Nanomedicine: Nanotechnology, Biology and Medicine.
“Treatment for breast cancer and other cancers often takes what is commonly called the ‘cut, poison and burn’ approach,” said John Mata, a senior research assistant professor of biomedicine in OSU’s College of Veterinary Medicine and lead author on the study. “Patients that are diagnosed with cancer are often treated by combinations of surgery, toxic chemotherapies and radiation.”
Nanotechnology – the use of tiny molecules that have been designed for specific tasks – to target tumors may provide a less invasive way of fighting cancer in humans and animals, according to Scott Gustafson, a veterinary surgeon and former OSU faculty member, who was a co-investigator on the study.
“Our demonstration of specific delivery of molecules used to diagnose tumors is an important step in the future of medical diagnosis and treatment using nanomedicine,” Gustafson said.
The researchers used a peptide called PAP-1 to target the cancer cells. The compound of 18 amino acids was developed by James Summerton, a former OSU biochemist and founder of Gene Tools, LLC of Philomath, Ore. The peptide is designed to activate when encountering the low pH levels produced within a growing tumor.
The key to the breakthrough was designing a peptide that would respond to low pH levels, the researchers say. Peptides that embed into membranes occur naturally; however, there are few examples in nature of peptides that will switch at very narrow pH ranges to do so. This is one of the first times that a peptide has been designed specifically as a delivery system for targeting cancer cells based on the unique physiology of tumors.
As tumor cells divide, they grow rapidly and use up the available blood supply creating hypoxia, or a low level of oxygen. The tumor cells also use more glucose than normal adjacent tissues. These differences can lead to acidic conditions and lower pH in the space between the cells within the tumor. As the nanotechnology-delivered molecules diffuse into the acidic area, it “throws on a chemical switch,” Mata said, directing the peptide to embed into the tumor cells.
“The peptide activates at a discrete pH and we believe that it could be used as a beacon to direct therapeutic antibodies to tumors,” Mata said. “Now that we have the ability to directly target the cells, the next step is to test antibodies and other therapeutic molecules for their ability to find and treat tumors.”
Attaching molecules to the peptide is not just a theory; the researchers already have used a radioactive element called technitium-99, which they bound to the PAP-1 peptide, to illuminate tumors in mice. The technique allowed the researchers to visualize the physical movement of their nanotechnology-delivered molecules in real-time using gamma scintigraphy. Additional studies demonstrated pH-specific activation using fluorescent probes attached to PAP-1.
“It also gave us a preliminary sense of how drug distribution may work, and how long it would stay in the system before excretion,” Mata said.
The work required a team of researchers from Gene Tools, LLC, and OSU’s Departments of Clinical and Biomedical Sciences (College of Veterinary Medicine), the Department of Pharmaceutical Sciences (College of Pharmacy) and the Department of Nuclear Engineering and Radiation Health Physics (College of Engineering).
The researchers say the technology should work with most solid tumors as long as they have areas with low levels of pH, which most tumors do. Though tested in mice, the results should be applicable to all mammals – including humans, Mata added.
The researchers say their studies also suggest the potential for using similar peptides as possible intervention for other conditions, including nerve regeneration in spinal cord injuries.
The research was funded by Gene Tools, LLC, and the Department of Defense.