Focused Ultrasound Shows Promise for Glioma Drug Delivery and Treatment

New research from UVA Health shows that brain tumors called gliomas may be even more receptive to targeted drug delivery using focused ultrasound than normal brain tissue, helping to allay concerns that tumor vasculature would make the approach ineffective. The technique uses tiny microbubbles activated by sound waves to open the brain's natural protective barrier — the blood-brain barrier — so drugs can enter exactly where needed.

In the study, researchers developed a high-resolution MRI protocol to track blood-brain barrier opening and molecular transport inside the tumor microenvironment. Rather than showing resistance due to chaotic tumor vasculature, glioma tissue demonstrated equal or superior receptivity to focused-ultrasound-mediated blood-brain barrier opening compared to healthy brain tissue. Delivery efficiency varied directly by molecular payload size: medium-sized drug molecules accumulated significantly more efficiently than either very small or oversized drug compounds, identifying a "Goldilocks" therapeutic size range. Focused ultrasound is non-invasive, using low-frequency acoustic waves to transiently and reversibly open the blood-brain barrier without requiring surgical incision or craniotomy.

Gliomas are the most common primary brain tumors in adults, including glioblastomas, the deadliest form of brain cancer. More than 10,000 people in the United States alone die from glioblastomas every year, and the tumors are almost always fatal within 5 to 10 years. In related early-stage work from the University of Virginia Comprehensive Cancer Center, scientists have developed an experimental approach using microRNAs that can simultaneously suppress multiple malfunctioning genes responsible for glioblastoma's formation and growth. The strategy combines brain-penetrating nanoparticles, focused ultrasound waves and microbubbles to deliver the miRNAs through the blood-brain barrier. In animal models, the miRNA slowed tumor growth and extended survival. The findings were published in JCI, the Journal of Clinical Investigation.

Researchers at Imperial College London are investigating a range of drugs in combination with low-intensity focused ultrasound in different subtypes of low-grade glioma in a preclinical model. Low-grade gliomas, classified as grade 2, are cancerous brain tumors that grow slowly at first but invariably progress to become high-grade, fast-growing tumors over time. The focused ultrasound is used to temporarily open the blood-brain barrier, giving medicines better access to the tumor.

Separately, a three-dimensional experimental system developed by the University of Trento, Bambino Gesù Children's Hospital and Sapienza University of Rome allows study of drug responses in low-grade glioma, a tumor of the central nervous system that often occurs in children. The researchers generated organoids from pluripotent stem cells and used them to develop the tumor. The organoids reproduce the molecular characteristics of low-grade gliomas in a slightly more faithful way than cells in single-layer culture and are more similar to patients' tumors. The results were published in the journal Molecular Cancer.

Brain tumors encompass more than 100 distinct tumor types, each with unique molecular and clinical characteristics. The standard of care for glioblastoma has remained largely unchanged for decades: surgical resection followed by radiation and temozolomide chemotherapy continues to be the dominant treatment option. The blood-brain barrier remains a primary obstacle, limiting the penetration of many small molecules and biologics into the central nervous system.