Using MRI-Guided Focused Ultrasound to Penetrate the Blood-Brain Barrier for Systemic Therapy
The Brain Tumor Stem Cell Research Lab at Mayo Clinic is investigating different pore (cavitation) parameters in the blood-brain barrier that would allow for the most human mesenchymal stem cell (hMSC) access to the brain with the least toxicity. Their research is aimed at identifying a novel way to treat glioblastoma without the need for surgery or for patients with inoperable tumors.
The blood-brain barrier poses a major limitation for chemotherapy agents to enter the brain. For glioma, the blood-brain barrier prevents therapy that is usually administered orally or intravenously from delivering the necessary drugs in effective concentrations.
The approach of Dr. Quinones-Hinojosa's team uses magnetic resonance-guided focused ultrasound (MRgFUS), in which MRI is utilized to locate the tumor and is coupled with pulses of low-intensity ultrasound frequency to provide focal enhanced delivery of hMSCs. This disruption causes targeted opening in the blood-brain barrier exactly where the tumor is located for increased concentration for brain tumor therapy.
Because the pore opening and tissue damage caused by MRgFUS can be unpredictable, and because the hMSCs packed with nanoparticles are relatively big, the Brain Tumor Stem Cell Research Lab is trying to come up with the right opening size and the right pulse that would cause the least damage while allowing for the greatest passage of hMSCs. Testing out target in situ pressure coupled with the optimal pulse intensity will increase drug-to-cell concentration and ultimately enhance therapeutic potential at the exact location of the tumor.
MRgFUS has previously been used clinically to deliver many different agents, such as chemotherapeutics, antibodies and nanoparticles. However, using a patient's own cells (hMSCs) to deliver the lab's nanoparticles, carrying poly(β-amino ester), or PBAE, biodegradable nanoparticles, is a novel way to guarantee the least toxicity and the highest drug amount at a concentrated area for patients with tumors that cannot be operated on or in critical regions in the brain that are too risky to resect with surgery.
Lab members studying the use of MRgFUS to penetrate the blood-brain barrier for systemic therapy include: