Determination of glioma cells’ malignancy and their response to TMZ via detecting exosomal BIGH3 by a TiO₂-CTFE-AuNIs plasmonic biosensor

Titanium dioxide (TiO₂) columnar thin film (CTF), coupled with gold nanoislands (AuNIs), greatly enhanced the performance of plasmonic sensing within the visible range by amplifying the localized plasmonic effect. Herein, this study reports a TiO₂-CTF enhanced-gold nanoislands (TiO₂-CTFE-AuNIs) localized surface plasmon resonance (LSPR) biosensor for the detection of glioma cells (GMs)-derived exosomes. The TiO₂-CTFE-AuNIs sensor chip was fabricated with an easy two-step anodization-annealing method, which could quantitatively detect GMs-derived exosomes via CD63 with the limit of detection (LOD) of 4.24 × 10⁻³ µg mL⁻¹. The sensitivity of this new plasmonic biosensor outperforms a self-assembled gold nanoislands (SAM-AuNIs) LSPR biosensor on CD63 detection by more than 2.5 times. Temozolomide (TMZ) has been proposed to cure malignant glioma, but post treatment diagnosis is still not fully successful. To address this issue, for the first time, the TiO₂-CTFE-AuNIs plasmonic biosensor was employed for the detection of BIGH3 in GMs-derived exosomes for tracking GMs’ malignant progression. It was found that this biosensor could quantitatively detect the dynamic change of exosomal BIGH3 in response to hypoxia and TMZ treatment with LOD of 3.84 × 10⁻³ μg mL⁻¹. This enables tracking of the level of BIGH3 in parent GMs, thus demonstrating TMZ’s anti-cancer effect. With excellently improved sensitivity, the TiO₂-CTFE-AuNIs real-time label‐free plasmonic biosensor shows great potential for its applications to the detection of prognostic biomarkers in GMs-derived exosomes for glioma liquid biopsy.