PO-204 Vascular effects of targeted photodynamic therapy of human glioblastoma with theranostic AGuIX nanoparticles

Abstract

IntroductionPhotodynamic therapy (PDT), a local and minimally invasive procedure for cancer treatment is a very promising approach in comparison to traditional forms of anticancer therapies. The aim of the study was to check the feasibility of functionalized AGuIX nanoparticles to act as a photosensitizer in photodynamic therapy against glioblastoma multiforme and its vasculature.Material and methodsChicken chorioallantoic membrane (CAM) model Human glioblastoma U87-MG xenografts were engrafted on CAM on embryo developement day 7. PDT treatment was applied in embryo development day 10. Effects of vasculature were investigated by fluorescence angiography.Mouse ectotopic tumourmodelU87-MG tumours were grown in Balb nude mouse legs. Effects on vasculature were investigated by USG with Doppler and PW mode (VEVO 2100), EPR oximetry and IHC.Mouse orthotopic tumourmodelU87-MG tumours were implanted in Balb nude mouse brains using stereotactic device. Effects on vasculature were investigated by MRI and IHC.PDTAGuIX photosensitizer solution in various doses was injected i.v. and after drug-light interval of 15 min and 1 hour tumours were irradiated with various light doses (λ=650 nm).Results and discussionsThere were visible changes in total vessel area, vessel density and size of vessels after photodynamic treatment in PDT-treated tumours, consistent with destruction of vasculature structure. Blood flow and blood flow velocity reflected a loss of vessel function in tumours and surrounding tissues after PDT with AGuIX nanoparticles.ConclusionVascular-targeted photodynamic therapy with AGuIX nanopartilcles led to vascular disruption of human glioblastoma xenografts in investigated animal models.