Vascular-Targeted Photodynamic Therapy (VTP)

International audienc

AGuIX® theranostic nanoparticles for vascular-targeted interstitial photodynamic therapy of brain tumors

International audienc

Gadolinium-based nanoparticles for the treatment of glioblastoma by MRI-guided photodynamic therapy

International audienc

Ultrasmall AGuIX theranostic nanoparticles for vascular-targeted interstitial photodynamic therapy of glioblastoma

International audienceDespite combined treatments, glioblastoma outcome remains poor with frequent local recurrences, indicating that a more efficient and local therapy is needed. In this way, vascular-targeted photodynamic therapy (VTP) is a promising complementary approach to improve tumor eradication1 by destroying its neovessels2. In this study, we designed a polysiloxane-based nanoparticle (NP) combining a magnetic resonance imaging (MRI) contrast agent, a photosensitizer (PS) and a new ligand peptide motif (KDKPPR) targeting neuropilin-1 (NRP-1)3,4, a receptor overexpressed by angiogenic endothelial cells of the tumor vasculature. This structure achieves the detection of the tumor tissue and its proliferating part by MRI analysis, followed by its treatment by VTP. The photophysical properties of the PS and the peptide affinity for NRP-1 recombinant protein were preserved after the functionalization of NPs. Cellular uptake of NPs by human umbilical vein endothelial cells (HUVEC) was increased twice compared to NPs without the KDKPPR peptide moiety or conjugated with a scramble peptide. NPs induced no cytotoxicity without light exposure but conferred a photocytotoxic effect to cells after photodynamic therapy (PDT)5. In vivo, complementary approaches were investigated, combining non-invasive imaging by magnetic resonance or by fluorescence and a tissue assay by ICP-MS to determine gadolinium concentrations, revealing renal and hepatic eliminations. The tumor selectivity of the NPs compared to the healthy brain parenchyma was validated by MRI data. The in vivo selectivity, evaluated using a skinfold chamber model in mice, confirms that the functionalized NPs with KDKPPR peptide moiety were localized in the tumor vessel wall, validating this vascular targeting strategy