BPS2025 - 3D-printed mini-brain/blood-brain barrier model for photothermal-mediated immunotherapy against glioblastoma

Glioblastoma multiforme (GBM) is the most lethal form of brain cancer, with a high incidence rate. The prognosis remains poor, even with surgery, radiotherapy, and chemotherapy. GBM's resistance to therapy stems from its heterogeneity and ability to evade immune detection. One major obstacle is the blood-brain barrier (BBB), which limits the delivery of therapeutic agents. Immunotherapy has emerged as a potential strategy, aiming to harness the immune system to target tumor cells. However, GBM's immunosuppressive environment has led to limited success in clinical trials. Non-invasive approaches, such as photothermal therapy (PTT), can play a key role in activating immune responses against cancer. Additionally, experimental models that replicate the complexity of GBM and its environment are lacking. A multidisciplinary approach that ensures BBB crossing, tumor targeting, and an efficient experimental model is crucial. Graphene quantum dots (GQDs), biocompatible light-responsive nanoparticles, show promise due to their ability to cross the BBB and convert light into heat. To test their efficacy we developed a 3D-bioprinted mini-brain model incorporating GBM. The model was integrated into a system with endothelial cells simulating the BBB. After administering GQDs and irradiating the GBM with an infrared laser, we observed a strong cytotoxic effect on tumor cells and immune cell activation towards cancer region. Our findings suggest that PTT can induce a strong and lasting immune response against GBM, enhancing the efficacy of immunotherapy using a reliable 3D-bioprinted model. We acknowledge financial support under the National Recovery and Resilience Plan (NRRP), Mission 4, Component 2, Investment 1.1, Call for tender No. 1409 published on 14.9.2022 by the Italian Ministry of University and Research (MUR), funded by the European Union - NextGenerationEU- Project titled, graphene quantum dots-mediated photoimmunotherapy against glioblastoma in a bioprinted mini-brain-on-chip - CUP J53D23017940001.