EFFICACY AND SAFETY OF DIRECT 1267 NM LIGHT THERAPY IN PRECLINICAL GLIOMA MODELS

Glioma is an aggressive brain tumour with limited therapeutic options and a poor prognosis. Light-based strategies such as photodynamic therapy (PDT) exploit the vulnerability of cancer cells to oxidative stress, largely mediated by singlet oxygen (¹O₂). Unlike conventional PDT, which depends on photosensitizers, we aim to use deep-penetrating 1267 nm laser irradiation to directly generate ¹O₂.
Therapeutic efficacy and safety of this strategy were evaluated through complementary in vitro and in vivo studies. Murine glioma cell lines GL261 and SMA560 were exposed to laser doses ranging from 450 to 1600 J/cm², followed by a PrestoBlue™ viability assay. Increasing irradiation induced a marked, dose-dependent reduction in viability in both cell lines, with SMA560 cells exhibiting greater sensitivity.
To assess treatment safety, identical laser doses were applied to mouse primary neuronal–astrocytic cortical co-cultures. Despite preserved cell viability, calcium imaging demonstrated dose-dependent functional impairments, with irradiation at 450, 900, and 1600 J/cm² reducing both the fraction of active cells and overall population activity compared with robust spontaneous activity in control cultures 24 hours post-treatment.
To support translational relevance, we established two in vivo mouse glioma models, VMDK and C57Bl6J mice, intracranially implanted with SMA560 and GL261 cells, respectively. Longitudinal magnetic resonance imaging is performed every five days, allowing for tumor growth monitoring over 20 days. These results will help to define the therapeutic window of 1267 nm direct light therapy. This work supports photosensitizer-free light therapy as a novel minimally invasive therapy for glioma.