Abstract
High grade gliomas are highly invasive tumors and surgery is therefore incapable of a cure. Despite post-operative radio/chemotherapy, glioblastomas (GBM) soon recur in almost 100 % of cases, with 80-90 % of tumor recurrence within 2 cm of the resected primary tumor. This infiltration most probably results from migration of tumor cells away from the tumor mass and into the normal brain parenchyma and/or a migration of tumor initiating stem cells distantly located from the tumor mass towards the resection site. Therefore, an important aim of post-operative treatment would be both inhibiting the migration of the nests of infiltrating tumor cells remaining at the margins of the resection cavity as well as the destruction of these cells. Ultrasonic activation of sonosensitizers, i.e., sonodynamic therapy (SDT) has been proposed as an alternative to light-activated PDT for the treatment of cancerous tumors including gliomas. The advantage of ultrasonic activation (SDT) versus light activation (PDT) is that ultrasound has a much lower tissue attenuation compared to visible light, allowing effective treatment to greater depths. In this project we have explored the ability of SDT to inhibit the invasiveness of glioma cells using an in vitro 3D spheroid migration assay. The results show that SDT significantly reduced the invasive potential of glioma cells in a 3D Matrigel migration assay, with higher sonication power correlating with decreased migration distances. This promising result suggests that SDT may offer a novel, non-invasive fractionated strategy to limit glioma infiltration, a major challenge in post-surgical tumor recurrence. However, further research is needed to optimize treatment parameters, investigate long-term effects, and validate these findings with in vivo models to assess translational potential.