Integrin targeted photodynamic therapy in patient‐derived glioblastoma spheroids

Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor, with a median overall survival of 14.6 months. GBM is incurable because of its invasive growth. These local invasive cells, most significantly glioblastoma stem cells (GSCs), when left behind, resist standard treatment, and cause almost all recurrences. However, the treatment of these infiltrative margins remains a significant challenge, as there are currently no options to reach these margins safely. Photodynamic therapy (PDT) shows promise as localized treatment option using light-activated compounds that target tumor cells and that generate reactive oxygen species (ROS) to destroy them. Far red light, combined with silicon phthalocyanines, could penetrate deeper making it more effective for reaching cancer cells in the tumor margin without compromise of healthy brain. In this study, we used patient-derived GBM spheroids in vitro as a preclinical model to evaluate a new dual-cRGDfK-silicon phthalocyanine conjugate targeting integrin αvβ3, a protein expressed by GBM cells and vasculature. Targeted PDT was efficient in killing GSC spheroids, showing that the combination of far-red light with more precise targeting can reach the type of cells found in the invasive margin, using silicon phthalocyanine as the photosensitizer.