Drug Delivery by Sonoporation in Childhood Diffuse Intrinsic Pontine Glioma and High-grade Glioma

Brain tumors in children contribute significantly to childhood cancer mortality. Diffuse intrinsic pontine glioma (DIPG) and pediatric high-grade glioma (pHGG) have a poor prognosis with a 5- year survival rate of <5% and 25 % respectively. Despite good effectiveness in the laboratory, chemotherapy shows limited efficacy in these brain tumor patients, as the blood-brain barrier (BBB) prevents these drugs from entering the brain. This project studies the potential of High Intensity Focal Ultrasound (HIFU) mediated BBB disruption using micro-bubbles present in the vascular system, in combination with anti-cancer drugs, in mice with DIPG and pHGG. A modeled (juvenile) human skull and mouse models will be used for HIFU modeling. HIFU allows temporary opening the BBB, potentially allowing more chemotherapy to reach the tumor site. Furthermore, by encapsulating effective medication in tiny bubbles (engineered PEG-liposomes) the BBB passage can be further optimized. This project aims to translate the innovative technologies MRg-HIFU and liposomal drug encapsulation to a better treatment for children with DIPG and pHGG.