A study using nanotechnology to treat brain tumors got such good results, the researchers initially questioned themselves. But further testing showed the results held up.
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Great discoveries do come in small packages. Few know that better than Ann-Marie Broome, Ph.D., who feels nanotechnology holds the future of medicine with its ability to deliver powerful drugs in tiny, designer packages.
Her latest research finds the perfect application -- targeting cancerous brain tumor cells.
Results from her recent paper published online in the international journal Nanomedicine - Future Medicine found that a lipid nanocarrier engineered to be small enough to get past the blood-brain barrier could be targeted to deliver a chemotherapeutic drug more efficiently to tumor cells in the brain.
In vivo studies showed specific uptake and increased killing in glial cells, so much so that Broome initially questioned the results.
"I was very surprised by how efficiently and well it worked once we got the nanocarrier to those cells," she said, explaining that initial results were so promising that she had her team keep repeating the experiments, using different cell lines, dosage amounts and treatment times."
Researchers and clinicians are excited because it potentially points the way to a new treatment option for patients with certain conditions, such as glioblastoma multiforme (GBM), the focus of this study.
Glioblastoma multiforme is a devastating disease with no curative options due to several challenges, said Broome, who is the director of Molecular Imaging of the Medical University of South Carolina's Center for Biomedical Imaging and director of Small Animal Imaging of Hollings Cancer Center.
The brain tumor has a significant overall mortality, in part due to its location, difficulty of surgical treatment and the inability to get drugs through the blood-brain barrier, a protective barrier designed to keep a stable environment within and surrounding the brain.
In 40 percent of cases, standard treatments will extend life expectancy 4 to 7 months. "It's really a dismal outcome. There are better ways to deliver standard of care."
That's where Broome and her nanotechnology lab enter in.
Nanotechnology is medicine, engineering, chemistry, and biology all bundled together and conducted at the nanoscale, between the range of 1 to 1,000 nanometers. For comparison, a thin newspaper page is about 100,000 nanometers thick.
Broome and her team took what they know about the cancer's biology and of platelet-derived growth factor (PDGF), one of numerous growth factor proteins that regulates cell growth and division and is also overexpressed on tumor cells in the brain.
With that in mind, they engineered a micelle that is a phospholipid nanocarrier, "a bit of fat globule," to deliver a concentrated dose of the chemotherapy drug temozolomide (TMZ) to the GBM tumor cells.
"Micelles of a certain size will cross the blood-brain barrier carrying a concentrated amount of TMZ," she explained about how the nanotechnology works.
"The PDGF is used much like a postal address. The micelle gets it to the street, and the PDGF gets it to the house." This targeting ability is important because researchers have learned that it's likely that the GBM will recur, she said.
"It's thought that satellite cells left behind after surgical removal are the fastest growing and most dangerous ones. We're trying to kill those rapidly growing satellite cells that will grow into new tumors in that location or others. These satellite tumors grow more aggressively than others. You have to hit them hard, fast and aggressively."
Surprisingly, nanotechnology is already a part of everyday life in many ways that people don't realize. It's used in everything from makeup as moisturizers or UV sunscreens to ice cream to maintain frozen temperatures and creamy textures.
In medicine, Broome said, researchers construct nanocarriers that are stable and stealthy. "Your immune cells can't attack them. They remain hidden."When the package gets to where it's going, nanotechnologists have various methods to get the micelles to release their payloads- one way is to use the acidic nature of a rapidly growing tumor."
In normal circulation, the pH of blood is slightly alkaline and the micelle stays intact. What researchers have discovered is that in many tumor types, the pH drastically changes to an acidic environment.
"While the tumor is growing, it creates waste by-products and metabolites that alter the pH, thus lowering it. As the center becomes more necrotic, it becomes even more acidic."
The change in pH triggers a release of the drug from our micelles just where clinicians want it to go to reduce toxicity to the rest of the body, she said.
"We take advantage of the tumor's natural environment as well as the cellular expression. I'm a big proponent of understanding that microenvironment has an impact on how well you can treat tumors.
"It's probably why so many therapeutics fail - because you have to take into account the immune system, the local environment, and the cells themselves - all three of these are important considerations."
That's why nanotechnology has an edge in shaping future cancer treatments. ■