Delta-24-RGD Induces Cytotoxicity of Glioblastoma Spheroids in Three Dimensional PEG Microwells.

Abstract

Glioblastoma (GBM) is the most aggressive brain tumor, with 12-15 months median survival time despite current treatment efforts. Among the alternative treatment approaches that have gained acceptance over the last decade is the use of replication-competent oncolytic adenoviruses, which are promising due to their relatively low toxicity and tumor-specific targeting. Three-dimensional (3D) tumor models can mimic the physiological microenvironment of GBM tumors and provide valuable information about the interaction between tumor cells and adenoviruses. Therefore, robust in vitro 3D tumor models are critical to investigate the mechanisms underlying tumor progression and explore the cytotoxicity effect of the adenovirus on tumor cells. In this study, we used a hydrogel microwell platform to generate in vitro 3D GBM spheroids and studied their interactions with the Delta-24-RGD adenovirus. The results showed that the cultured 3D spheroids were successfully infected by the Delta-24-RGD. A significant cell lysis was observed. Cell viability was decreased approximately 37%, 54% and 65% with 10, 50, and 100 MOIs, respectively. The infection of the Delta-24-RGD was found more effective on 3D spheroids when compared to 2D monolayer cell culture. These results implicate that our hydrogel microwell platform could provide a promising 3D model to investigate the oncolytic potential of the viruses in vitro.