In Vitro Sonodynamic Therapy Using a High Throughput 3D Glioblastoma Spheroid Model with 5‐ALA and TMZ Sonosensitizers

Sonodynamic therapy (SDT) administered using low-intensity pulsed ultrasound and sonosensitizers is an emerging, minimally invasive, targeted deep-tissue therapy for solid tumors such as glioblastoma multiforme (GBM). Initial clinical trials show promising outcomes for SDT treatments of GBM. A crucial aspect of SDT is the sonosensitizer that interacts with ultrasound, facilitating energy transfer to the tumor, thus inducing therapeutic efficacy. Current in vitro methods for determining the therapeutic efficacies of sonosensitizers are time-consuming and expensive. A novel high-throughput magnetically printed 3D GBM model is used to overcome this challenge. The hypothesis is that the use of two sonosensitizers, one a chemotherapeutic drug, enhances SDT efficacy through their additive chemical interactions. The GBM model is used to evaluate the effectiveness of two sonosensitizer molecules, 5-aminolevulinic acid (5-ALA) and theU.S. Food and Drug Administration (FDA)-approved chemotherapeutic drug Temozolomide (TMZ). It is confirmed that implement high-throughput GBM models to evaluate sonosensitizer combinations and their efficacies is feasible and, for the first time, show that the combined effect of both sensitizers, 5-ALA and TMZ, is superior for preventing spheroid growth than employing each molecule separately. This finding is relevant for future clinical trials of GBM treatment with SDT.