Combining a common chemotherapy drug with an experimental nanotechnology allowed the drug to cross the blood-brain barrier and increased the survival rate in a mouse model of glioblastoma up to 50%, a team led by researchers from UT Southwestern Medical Center and UT Dallas found. Their research, published in Nature Communications, could lead to possible new treatments for glioblastoma, the most common and aggressive primary brain tumor.
“The biggest barrier to effectively treating glioblastoma has always been getting chemotherapies into the brain. This new approach could be a game changer for this disease,” said corresponding author Robert Bachoo, M.D., Ph.D., Associate Professor of Neurology and Internal Medicine and a member of the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern. Zhenpeng Qin, Ph.D., Adjunct Associate Professor of Biomedical Engineering at UTSW and an Associate Professor at UT Dallas, also was a corresponding author.
Despite decades of research, the prognosis for glioblastoma patients remains dismal; their median survival rate is about 15 months after diagnosis. Although surgery can remove the primary tumor, glioblastoma almost universally returns due to cancerous cells that spread beyond the tumor’s visible margins.
The biggest obstacle to killing these cells is the blood-brain barrier (BBB), proteins that form tight junctions between cells that line the brain’s blood vessels and prevent potentially toxic molecules from entering the brain. Although many chemotherapy drugs are effective against glioblastoma cells in petri dishes, Dr. Bachoo explained, the BBB prevents these drugs from reaching glioblastoma cells in patients and animal models.
Researchers have explored several strategies to open the BBB, but each has significant risks, including excessive toxicity and heat damage.
In the new study, Dr. Bachoo and his colleagues tested a new approach: gold nanoparticles coated with antibodies against a key protein in the BBB complex, a strategy they named optoBBTB. When these nanoparticles are injected intravenously in animal models, they migrate and attach to the tight junction proteins. A precise wavelength of laser light can cause these nanoparticles to vibrate, opening the BBB without generating heat.
The researchers worked with two types of genetically engineered mice that have mutations found in human glioblastoma patients and recapitulate key features of glioblastoma. When the researchers delivered optoBBTB to mice of either type, dye injected shortly afterward infiltrated the animals’ tumors, suggesting this strategy successfully breached the BBB.
