"Effects of Redox Status on Immediate Hypericin-Mediated Photodynamic Therapy in Human Glioblastoma T98G Cell Line"

ACS Omega. 2024 Dec 28;10(1):1100-1109. doi: 10.1021/acsomega.4c08553. eCollection 2025 Jan 14.

Abstract

Glioblastoma Multiforme (GBM) is one of the most aggressive types of brain tumor. GBM can modulate glutathione (GSH) levels and regulate cellular redox state, which can explain its high resistance to chemotherapeutic agents. Photodynamic therapy (PDT) is a selective, nontoxic, and minimally invasive treatment approved for many types of cancer. PDT leads to cell death mainly by promoting the generation of reactive oxygen species (ROS). Thus, in the current study, PDT with the photosensitizer hypericin (Hyp), formulated in mixed 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC)/biotinylated-pluronic F127 (F127-B) liposomes, in combination with the GSH synthesis inhibitor buthionine sulfoximine (BSO) were tested against T98G cell line of human glioblastoma. The mixed liposome was effective in delivering Hyp to the cells, leading to a dose relationship between Hyp and ROS levels. BSO potentiated Hyp cell uptake, decreased GSH levels regardless of Hyp concentration, and intensified ROS generation for 1.00 and 5.00 μmol L-1 Hyp. Nonetheless, cell death was more pronounced in the groups not treated with BSO, indicating that reduced GSH levels are not a decisive factor in achieving the PDT effects of Hyp. In conclusion, the mixed DPPC/F127-B liposomes were effective as a delivery system for Hyp. However, the combination of BSO and Hyp was not capable of optimizing PDT against T98G cells.