The blood-brain barrier, which bars the passage of certain substances from the blood to the brain, has long posed a challenge to treating many brain disorders. Ann-Marie Broome of the Medical University of South Carolina has identified a lipid nanocarrier small enough to bypass the barrier and potentially deliver chemotherapy more efficiently to the brain.
Focusing on glioblastoma multiforme, a fast-growing and difficult-to-treat brain cancer, Broome's team used the platelet-derived growth factor (PDGF) of the cancer as a target for the chemotherapy drug temozolomide, the university said in a statement. The phospholipid nanocarrier, which Broome called a “bit of fat globule,” gets the drug across the barrier, while the PDGF gets it to the tumor. The results, published in Future Medicine, showed drug uptake and increased killing in glial cells, which are supportive cells in the central nervous system.
Once the nanocarrier gets to its destination, the acidic environment of the tumor causes it to release its payload. It doesn’t release the drug while in the bloodstream, which is normally slightly alkaline.
“We take advantage of the tumor’s natural environment as well as the cellular expression,” Broome said in a university news release. “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.”
After perfecting this delivery mechanism, collaborator Dr. Amy Lee Bredlau, director of MUSC Health’s Pediatric Brain Tumor Program, envisions a treatment that will have better cure rates and reduce “a huge portion” of chemotherapy side effects. But Broome warned that it’s still early days and much work is ahead before new options will be made available to patients.
“It may or may not be effective for all types of GBMs,” Broome said in the release. "There are subtypes as well as therapeutic-resistant GBMs that these nanocarriers may not impact. We need to continue rigorous testing to verify and validate our initial findings.