Toward the Treatment of Glioblastoma Tumors Using Photoactivated Chemotherapy: In Vitro Evaluation of Efficacy and Safety

Glioblastoma multiforme (GBM) is highly aggressive, necessitating new therapies. Photoactivated chemotherapy (PACT) offers a promising approach by activating prodrugs with visible light at the tumor site. This study evaluated the anticancer activity of ruthenium-based PACT compounds in U-87MG glioblastoma cells and their safety in SH-SY5Y neuron-like cells. The compound [3](PF6)2 showed promising light-activated anticancer effects in U-87MG cells, while [1](PF6)2 was inactive, and [2](PF6)2 was nonactivated. Interestingly, in SH-SY5Y cells, light-activated [3](PF6)2 increased cell proliferation, similar to donepezil, without causing cell death. Increased Ca2+ uptake was observed, possibly via interaction with the AMPA receptor, as suggested by docking studies. These findings suggest ruthenium-based PACT compounds may serve as potential treatments for GBM, effectively attacking cancer cells while preserving healthy neuronal cells.