Targeted, Rationally Designed Nanoparticle Therapeutics for Pediatric Medulloblastoma
Abstract
Dr. Straehla is a pediatric oncologist in training who specializes in the treatment of pediatric brain tumors. She is enrolled in the hematology/oncology fellowship training program at the Dana-Farber/Boston Children s Cancer and Blood Disorders Center and is currently completing a postdoctoral fellowship at the Massachusetts Institute of Technology. She chose to pursue a research opportunity under the mentorship of Dr. Paula Hammond at the Koch Institute for Integrative Cancer Research to hone her engineering skills in order to develop new therapies for pediatric patients with brain tumors. While caring for pediatric brain tumor patients during her training, she was alarmed at how little is known about drug delivery into the brain. The standard treatment for pediatric brain tumors was developed by trial-and-error over the last 40 years, and very little has changed. In the case of medulloblastoma, the most common brain tumor in school-aged children, patients first have an aggressive brain surgery to remove as much of the tumor as possible, and then receive drugs and radiation that act by killing any dividing cells. For most drugs, less than 5% is delivered into brain tissues, meaning that many healthy cells must be killed in order to treat the tumor effectively. The goal of Dr. Straehla’s project is to design a specialized nanoparticle to bring drugs selectively to brain tumors in order to more effectively treat the tumor while sparing normal tissues. These nanoparticles are quite small – about 100 nanometers, or about the size of a virus. In the center is a core particle that can hold drugs. The core is then wrapped in interchangeable layers that influence its trafficking in the body and interactions with cells. Her project includes testing a methodical collection of nanoparticles in order to find a combination that crosses the blood-brain-barrier and penetrates deep into medulloblastoma tumors. Ultimately, this medulloblastoma-targeted nanoparticle can be loaded with drugs that do not cross into the brain readily on their own. The technology has the potential to increase cure rates for medulloblastoma by bringing drugs to the tumor where they are most effective. It also has the potential to change the paradigm of treatment. For example, rather than relying on radiation, which kills normal cells as well as tumor cells and decreases IQ, memory, and processing speed, the targeted nanoparticles could be loaded with specialized radiation-inducing drugs that only cause damage to the cells immediately around them. The design of the nanoparticle makes it extremely versatile, as nearly any drug or therapy could be packaged inside. The proposed research will validate the trafficking and delivery capabilities of the nanoparticle system. If successful, the platform will be loaded with a drug and moved forward to pre-clinical testing, with potential to impact patients in the next 5 to 7 years and could help doctors and researchers change the way pediatric brain tumors are treated. Not only will more children survive brain cancer, their quality of life will be drastically improved compared to survivors of the current treatments. Future applications of the proposed research include expanding the platform to target other brain cancers such glioblastoma multiforme, a common brain tumor in adults, as well as cancers that have spread to the brain from other places in the body. This is highly relevant to military members and their families, especially in light of recent evidence suggesting an increased risk of cancer for veterans who have served overseas in areas with increased exposure to carcinogens. The development of new therapies for brain cancer is urgently needed and a solution will positive effect society at large.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jul 16, 2019
- Source ID
- W81XWH1910252
Entities
People
- Joelle Straehla
Organizations
- Massachusetts Institute of Technology
- United States Army