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It's simple mechanics - going through a doggy door is not a challenging task for a tiny puppy, but it is fairly difficult for a larger human. 

Associate Professor of Engineering Thomas Webster and Lijuan Zhang GS have found an important application of this simple fact, creating surfaces that prevent cancer cells from growing on the body's tissues but allow healthy cells to thrive. In this scenario, in which cancer cells are the large humans and healthy cells are the puppies, healthy cells can navigate through areas that stiff and rigid cancer cells cannot.

In a paper published last month in the journal Nanotechnology, Webster and Zhang describe the application of nanotechnology, the development of extremely small materials one billionth the size of a meter, to novel therapies for breast cancer.

According to the American Cancer Society, one in eight women in the United States will develop some form of breast cancer. Eleven percent of these women have a recurrence of their cancer within five years and 20 percent have one within 10 years. These women often undergo various forms of surgery to remove the tumor, including removal of one or both breasts. Many women choose to undergo breast reconstruction at some point after their surgery, often with the use of implants.

Webster and his team decided to modify existing materials for breast implants by changing the patterns on their surfaces. They have developed implants with novel "nanofeatures" - small lumps and bumps of selected height and width ­- that are hostile to tumor cells but friendly toward healthy cells. By modifying the architecture of the implants, Webster and his team have been able deter cancer cell growth.

Webster said the idea for creating these nanofeatures came from observing trends in nature. Prior to coming to Brown, Webster studied patterns of natural surface of tissues in human cadavers.  

"The body constantly creates natural nanoparticles," Webster said. "Oftentimes, the biomaterials we implant into patients, such as hip implants, look nothing like natural tissue on the nano scale. These artificial implants have a smooth texture, but natural tissue is bumpy."

Webster and Zhang sought to recreate the body's natural bumpy surfaces by using polystyrene beads 23 nanometers in diameter and polylactic-co-glycolic acid, a federally approved biodegradable polymer. The surfaces they created had "nooks and crannies" that healthy cells were flexible enough to navigate through, but stiff cancer cells could not.

"The surfaces we created kept stiff cancer cells levitating above the surface, allowing pliable healthy cells to grow underneath," Webster said. "Healthy cells love the environment we're creating, but cancer cells don't."

Webster and his team have had similar successes in cancer cells of both lung and bone, and the group's research on selective death of cancerous cells using breast cancer implants has been ongoing for the past four years.

Ryan Wylie, a researcher at the Laboratory for Biomaterials and Drug Delivery at Children's Hospital Boston in conjunction with the Langer Lab at the Massachusetts Institute of Technology, called Webster and Zhang's research "a new spin on nanotechnology for cancer."

Though most research is focused on the delivery of drugs using nanoparticles, "these researchers have shown that nanotechnology will be useful to treat cancer beyond the traditional methods commonly discussed in the field," Wylie said.

"Cancer cells usually win. We're turning the tide in the opposite direction, and healthy cells now have an advantage," Webster said.

Webster said the next step is to test the nanofeature implants in animals and partner with industry to take the technology to the next level.

Webster's group is also planning on testing other polymers, such as silicone, to see if they yield similar results in decreasing cancer cell growth. There are a variety of materials federally approved for implantation and reconstruction in humans, and Webster hopes to change the surface patterns of each using nanotechnology.  

"A lot of people think that nanotechnology is foreign and new, but we are finding that natural nanostructures have been around as long as Earth itself," Webster said, adding that nanostructures exist in everything from asteroids to coral reefs.

Webster said the idea to use nanoparticles specifically for breast cancer was Zhang's idea. The team had to educate themselves about current implant materials and faced challenges in "getting up to speed with breast cancer biology."

In the future, the group plans to examine smaller nanostructures, with the belief that the smaller the structure, the more effective it might be.




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