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

in ACS pharmacology & translational science by Sina Katharina Goetzfried, Matthijs L A Hakkennes, Anja Busemann, Sylvestre Bonnet

TLDR

  • Ruthenium-based photoactivated chemotherapy compounds show promise in treating glioblastoma multiforme by selectively targeting cancer cells.

Abstract

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 [](PF)showed promising light-activated anticancer effects in U-87MG cells, while [](PF)was inactive, and [](PF)was nonactivated. Interestingly, in SH-SY5Y cells, light-activated [](PF)increased cell proliferation, similar to donepezil, without causing cell death. Increased Cauptake 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.

Overview

  • The study evaluated the anticancer activity of ruthenium-based photoactivated chemotherapy (PACT) compounds in U-87MG glioblastoma cells and their safety in SH-SY5Y neuron-like cells.
  • The compounds were activated with visible light at the tumor site, offering a promising approach for treating glioblastoma multiforme (GBM).
  • The primary objective was to investigate the effectiveness of ruthenium-based PACT compounds in selectively targeting cancer cells while preserving healthy neuronal cells.

Comparative Analysis & Findings

  • Compound [](PF) showed promising light-activated anticancer effects in U-87MG cells, while [](PF) was inactive, and [](PF) was non-activated.
  • In SH-SY5Y cells, light-activated [](PF) increased cell proliferation, similar to donepezil, without causing cell death.
  • Increased cell uptake was observed, possibly via interaction with the AMPA receptor, as suggested by docking studies.

Implications and Future Directions

  • Ruthenium-based PACT compounds may serve as potential treatments for GBM, effectively attacking cancer cells while preserving healthy neuronal cells.
  • Further studies are needed to fully understand the mechanisms of action and potential off-target effects of these compounds.
  • The development of these compounds could lead to the creation of new therapies for GBM and possibly other cancer types.
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