Preclinical Photodynamic Therapy Targeting Blood Vessels with AGuIX® Theranostic Nanoparticles

Abstract

Background: Glioblastoma multiforme (GBM) is the most common highly aggressive, primary malignant brain tumor in adults. Current experimental strategies include photodynamic therapy (PDT) and new drug delivery technologies such as nanoparticles, which could play a key role in the treatment, diagnosis, and imaging of brain tumors. Objectives: The purpose of this study was to test the efficacy of PDT using AGuIX-TPP, a polysiloxane-based nanoparticle (AGuIX) that contains TPP (5,10,15,20-tetraphenyl-21H,23H-porphine), in biological models of glioblastoma multiforme and to investigate the vascular mechanisms of action at multiple complexity levels. Methods: PDT effects were studied in monolayer and spheroid cell culture, as well as tumors in chicken chorioallantoic membranes (CAMs) and in mice were studied. Results: Treatment was effective in both endothelial ECRF and glioma U87 cells, as well as in the inhibition of growth of the glioma spheroids. PDT using AGuIX-TPP inhibited U87 tumors growing in CAM and destroyed their vascularization. The U87 tumors were also grown in nude mice. Their vascular network, as well as oxygen partial pressure, were assessed using ultrasound and EPR oximetry. The treatment damaged tumor vessels and slightly decreased oxygen levels. Conclusions: PDT with AGuIX-TPP was effective against glioma cells, spheroids, and tumors; however, in mice, its efficacy appeared to be strongly related to the presence of blood vessels in the tumor before the treatment.