Glioblastoma targeting by water-soluble hypericin derivate HHL-PVP and photodynamic tumour killing.

Hypericin, a tumour-selective photosensitizer, has shown potential in cancer therapy, but its poor water solubility has limited clinical use. To address this, we developed a water-soluble variant called high hypericin-loaded polyvinylpyrrolidone (HHL-PVP) to enhance hypericin's applicability, particularly for treating glioblastoma, a typically terminal disease. We tested HHL-PVP in both in vitro and in vivo models, first confirming its fluorescent properties in the lab and then assessing its efficacy in more complex animal models. Using subcutaneous and orthotopic tumour mouse models, we combined HHL-PVP administration with fluorescence-guided surgery and photodynamic therapy (PDT) to target residual tumour cells. Histological analysis of both healthy and tumour tissue showed HHL-PVP's over 97 % sensitivity and 100 % specificity in distinguishing tumour tissue. In subcutaneous glioblastoma models, significant tumour necrosis and remission occurred after HHL-PVP administration and a 20-minute white light application through the skin. These results highlight HHL-PVP's effectiveness in targeting and eradicating glioblastoma cells. Our findings provide strong evidence that HHL-PVP is a promising therapeutic option for glioblastoma, with its high sensitivity, specificity, and potential for tumour remission through PDT. This approach warrants further investigation in clinical trials and could improve outcomes for a disease that has been difficult to treat.