BPS2025 - Photothermal therapy mediated by graphene quantum dots increases drug permeability in 3D glioblastoma models

Graphene quantum dots (GQDs) are biocompatible nanoparticles used in the biomedical field due to their small size and unique photophysical properties. Notably, GQDs can traverse biological barriers, including the blood-brain barrier, making them promising candidates for brain disease therapies. Studies have shown that surface-functionalized GQDs improve membrane fluidity and increase intracellular uptake, creating a synergistic effect with antitumor drugs at subtherapeutic doses. In this study, we examined the effects of GQDs in combination with the chemotherapeutic agents doxorubicin and temozolomide on a complex 3D spheroid model of glioblastoma. Our findings revealed that GQDs' ability to absorb and convert near-infrared light into heat plays a crucial role in enhancing membrane permeability in this 3D model. This non-invasive approach, known as photothermal therapy (PTT), when combined with chemotherapy at subtherapeutic doses, significantly boosted the antitumor effects, reducing tumor growth and viability. Our results suggest that increasing membrane permeability through GQDs can enhance the effectiveness of antitumor drugs at lower doses, potentially minimizing side effects, stimulating immune response, and ultimately improving patient quality of life. 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 B53D23031470001.