서강대학교

초록 (요약문)

Glioblastoma (GBM) is the most commonly occurring malignant brain tumor of the central nervous system. Several studies have suggested various three-dimensional (3D) models that mimic the microenvironment of human GBM. However, current in vitro GBM models are still limited by the lack of useful 3D biosensing system to detect 3D models for drug evaluation. In this study, we developed a GBM biosensing system with a flexible electrochemical biosensor to detect L-glutamate released from a CRISPR/Cas9-engineered organoid model of human GBM. To recapitulate the structural and functional features of the brain tumor, a 3D GBM model was established by inducing specific genetic mutations with a combination of clinically frequent aberrations (NF1–/–, PTEN–/–) via CRISPR/Cas9. Our biosensing system for drug screening was fabricated using flexible Au electrodes on a polymer substrate and concave PDMS, capable to increase the contact area between organoids and Au electrodes while making 3D interfaces. Also, glutamate oxidase (GmOx) was immobilized for selective detection of L-glutamate. This biosensor successfully detected L-glutamate present higher in GBM organoids than naïve cerebral organoids. Additionally, we evaluated the anti-tumor drug effects on GBM organoids by comparing the L-glutamate concentrations detected via this biosensor. The proposed system will be widely applied as a GBM biosensing system that can be utilized to explore brain tumors derived from specific driver mutations, which might allow personalized therapy for brain tumor diseases.