Researchers at the Massachusetts Institute of Technology demonstrated in an animal study that nanoparticles shuttling two different cancer drugs could effectively cross the blood-brain barrier and target tumor cells.
The team of scientists evaluated the drug combination in mice that had gliobastoma – an aggressive form of brain cancer that is notoriously hard to treat.
The researchers loaded liposomes with two drugs: one in the particle’s outer shell and one inside the particle’s inner core. Then, they coated the liposomes with a transferrin, a protein designed to help send the particles through the blood-brain barrier and aggregate at the site of the tumor.
“What is unique here is we are not only able to use this mechanism to get across the blood-brain barrier and target tumors very effectively, we are using it to deliver this unique drug combination,” senior author Paula Hammond told MIT News.
The researcher chose to combine a chemotherapy drug, temozolomide, with an investigational bromodomain inhibitor. Because their delivery approach targeted tumor cells, the scientists didn’t need to worry about the toxic side effects associated with systemic administration of temozolomide.
Researchers hypothesize that bromodomain inhibitors interfere with a cell’s ability to repair damage to its genetic makeup. Together, the temozolomide and the bromodomain inhibitor worked to interrupt the cell’s DNA-repair mechanism and then directly attack the cell’s DNA.
In a mouse study published in Nature Communications, the MIT researchers showed that the nanoparticles’ outer layer degrades once the liposomes reach the tumor cells, delivering the bromodomain inhibitor. After 24 hours, temozolomide is unleashed from the particle’s inner core.
Beyond proving that their drug-delivery method was effective, the researchers also showed that the nanoparticles coated with transferrin were more powerful than other treatments – the mice treated with transferrin-coated particles lived twice as long as the mice that were treated with uncoated particles or injected with temozolomide or the bromodomain inhibitor.
“This was really a proof-of-concept study [showing] that we can deliver novel combination therapies using a targeted nanoparticle system across the blood-brain barrier,” lead author Fred Lam said, according to MIT News.