A dual-wavelength blue laser platform for integrated diagnosis and therapy in glioblastoma: preclinical evidence

Glioblastoma (GBM) remains clinically intractable owing to dismal prognosis and frequent recurrence. This study aimed to develop a dual-wavelength blue laser platform (450 nm and 405 nm) that integrates laser ablation, photodynamic diagnosis (PDD), and photodynamic therapy (PDT) in preclinical models, with 405 nm designated for PDD and 450 nm for PDT. Ex vivo ablation and coagulation were performed on porcine brain tissue using a 450 nm laser, compared with a conventional 980 nm laser or bipolar forceps. Subcutaneous and orthotopic GBM mouse models were used to assess 405 nm irradiation for tumor visualization following 5-aminolevulinic acid (5-ALA) administration. In vitro and in vivo experiments evaluated the therapeutic efficacy of 450 nm laser-mediated PDT, with 630 nm laser-mediated PDT serving as the positive control. Tumor recurrence was assessed after surgical resection combined with PDT. The 450 nm laser produced deeper and narrower incisions with less thermal coagulation than the 980 nm laser or bipolar forceps. 405 nm irradiation enabled clear tumor visualization, with peak 5-ALA-induced fluorescence at 2 h post-administration in subcutaneous tumors and 4 h in orthotopic tumors. The 450 nm laser induced concentration-dependent cytotoxicity in GBM cells and elicited robust photodynamic effects. Notably, surgical resection followed by PDT significantly suppressed tumor recurrence. These results validate an integrated strategy that uses a 405 nm laser for intraoperative PDD and a 450 nm laser for precise ablation and subsequent PDT, positioning this dual-wavelength blue laser platform as a promising, comprehensive approach to improving GBM surgical outcomes.