A novel strategy for the photothermal treatment and electroencephalogram monitoring of in situ glioma

Abstract

The current photothermal treatments for glioma suffer from inappropriate tumor models, nanoparticle-related long-term intracranial retention, and the absence of real-time electroencephalography monitoring. Herein, we report the development of an integrated photothermal therapy (PTT)-electroencephalogram (EEG) monitoring system based on micropyramid-structured polypyrrole (m-PPy) film patches, enabling the accurate and controllable treatment of intracranial gliomas in situ while providing the real-time monitoring of intraoperative complications. The pyramid architecture of the m-PPy film endows it with excellent photothermal conversion efficiency and electrochemical behavior, which allow it to simultaneously function as a photothermal agent for tumor ablation and a bioelectrode for electroencephalography signal collection. The flexible and stretchable nature of m-PPy allows it to adhere well to tumors for preventing glioma rupture while obtaining stable signal acquisition. More importantly, it can be completely removed after surgery to prevent the long-term toxicity caused by intracranial residues. In vitro experiments suggest that it induces C6 glioma cell apoptosis through the upregulation of Anxa5 and Csrp3 coupled with the downregulation of septin-4, effectively activating the apoptotic pathway. In orthotopic tumor models, the integrated system achieves complete tumor ablation while simultaneously monitoring intraoperative neuroelectrophysiological changes in real-time through EEG (via the dynamic analysis of the α/θ/β wave power spectra), achieving a temperature control accuracy of ±0.8 °C mm⁻¹. Proteomic analysis revealed that PTT significantly inhibits tumor migration by suppressing mitochondrial complex I (as evidenced by the downregulation of NDUFB2/4) and motor protein pathways. Hence, this platform overcomes critical barriers in glioma therapy by eliminating invasive procedures while ensuring the real-time detection of treatment complications.