Treating tumors at the molecular level

Like many life-threatening diseases, brain tumors originate from altered biological processes at the molecular level. Nanomaterials — generally consisting of metal or nonmetal atoms or a mixture of both — are similar in scale to biological molecules and systems and can be engineered to carry out various functions.

At Mayo Clinic in Jacksonville, Florida, researchers are investigating ways to use the physical properties and characteristics of nanomaterials to diagnose and treat diseases at the molecular level. The Mayo scientists see great potential in nanoparticles as a means of not only delivering drugs to tumors but also changing the tumor microenvironment.

"In 10 years I envision a boom in nanoparticles for medical purposes. We are going to develop very smart, targeted devices," says Betty Y S (Betty) Kim, M.D., Ph.D., a neurosurgeon at Mayo Clinic's campus in Florida. "In addition to using nanomaterials as a Trojan horse to deliver medication to disease sites, I foresee using the physical properties these materials possess in the nanoscale to monitor cell function and halt tumor progression."

What true nanoparticles can do

Although nanomaterials have attracted great attention, Dr. Kim cautions that they are sometimes incorrectly defined in the literature. "In the strictest sense, nanotechnology deals with materials in the nanoscale of 1 to 100 nanometers," she says. "Above that range, you can't fine-tune the optical or magnetic or other physical properties that are unique to nanomaterials."

Those properties are the source of nanoparticles' therapeutic benefits. Because of their small size, and scientists' abilities to alter their surface chemistry, nanoparticles can cross the blood-brain barrier, facilitating delivery of chemotherapy into the central nervous system. Nanomaterials also have a high ratio of surface area to volume, allowing nanoparticles to carry a big payload.

"We can attach antibodies or peptides on the surface of these structures to target a particular cancer cell or stroma so that the nanoparticles reach the site of interest. We can also attach medications and potentially fluorescent probes that would allow us to see what is happening at the cellular level," Dr. Kim says. "The fact that we can use a very small particle but have this tremendous surface area to play with is a huge advantage."

Engineering the tumor microenvironment

Another focus of Dr. Kim's research is the potential use of nanoparticles to change the tumor microenvironment. Because tumor cells constantly mutate, they become resistant to therapy. The tumor itself acts to suppress immune cells attempting to fight the tumor process.

"I think we can use nanoparticles to study which specific cells are involved in this process and re-engineer those cells using nanomaterials to allow the immune system to be less suppressed," Dr. Kim says. "The goal is to make the immune system an anti-tumor state."

Blood vessels in the tumor might also be re-engineered to co-opt them into fighting the cancer. The vessels that develop within tumors are physically abnormal, resulting in poor blood flow that limits the amount of medication reaching the tumor. "If we can re-engineer the blood vessel formation so that the vessels are a little more normal, they could be the highways along which we will deliver our cancer medications," Dr. Kim says.

Biobank and personalized care

In line with its commitment to nanotechnology, Mayo's campus in Florida is also significantly expanding its tumor biobank — an initiative begun by Mayo researchers Kurt A. Jaeckle, M.D., Robert E. Wharen Jr., M.D., and Panagiotis Z. Anastasiadis, Ph.D., through the generosity of the JLG Brain Cancer Foundation. The biobank contains not only tumor tissue, from which DNA and RNA are extracted for analysis, but also blood samples taken from patients prior to any incisions.

Dr. Kim foresees a time when blood markers will be used to differentiate tumors and individualize therapies. "We don't have the technology to do that yet. But within the next few years, I think we will be able to code all of these tumors in ways that allow us to provide targeted, personalized therapies," she says. "Nanotechnology will definitely bridge that gap."