Microscope-Guided Photo-Theranosis of Malignant Brain Tumors: A Proof-of-Concept Study

Abstract

BACKGROUND The infiltrative nature of malignant brain tumors, such as glioblastoma, complicates complete surgical resection and leads to high recurrence rates. We developed a novel microscope-guided photo-theranosis system to precisely identify and simultaneously treat tumor tissues while minimizing damage to surrounding normal tissue. This study provides a proof-of-concept for this innovative therapeutic strategy.

METHODS Human U87MG and U87MG-GFP glioblastoma cells were used in cultures and spheroids. Diagnostic capability of the system was validated by detecting GFP fluorescence, while therapeutic efficacy was assessed by applying region-selective photodynamic therapy (PDT) with a 595 nm LED. Hypericin was used as a photosensitizer, with its delivery confirmed via fluorescence imaging. For in vivo studies, an orthotopic xenograft mouse model was established using U87MG-GFP cells. Following craniotomy, the exposed tumor underwent an intraoperative photo-theranosis procedure: 1) tumor scanning, 2) region of interest (ROI) selection, and 3) masked PDT on the selected ROI to evaluate its performance.

RESULTS The system successfully identified tumor regions via GFP fluorescence and demonstrated the capability for selective PDT. In vitro, the PDT-treated group showed statistically significant inhibition of spheroid tumor growth compared to the non-PDT control group (mean relative volume: 1.089 ± 0.717 vs. 2.496 ± 0.992, respectively; p < 0.05). In the brain tumor animal model, the system effectively scanned the post-craniotomy tumor and enabled user-defined, ROI-specific PDT, thus validating its feasibility for intraoperative application.

CONCLUSIONS The microscope-guided photo-theranosis system suggests a new paradigm for treating malignant brain tumors by enabling real-time, accurate diagnosis and concurrent therapy. This technology has the potential to become an innovative intraoperative strategy that maximizes tumor control while minimizing damage to healthy tissue, offering a significant advancement in neuro-oncological surgery.