Ultrasmall AGuIX theranostic nanoparticles for vascular-targeted interstitial photodynamic therapy of glioblastoma.
Fiche publication
Date publication
janvier 2017
Journal
International journal of nanomedicine
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BARBERI-HEYOB Muriel, Dr FROCHOT Céline, Dr VANDERESSE Régis, Pr BOURA Cédric, Dr THOMAS Noémie
Tous les auteurs :
Thomas E, Colombeau L, Gries M, Peterlini T, Mathieu C, Thomas N, Boura C, Frochot C, Vanderesse R, Lux F, Barberi-Heyob M, Tillement O
Lien Pubmed
Résumé
Despite 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) could help tumor eradication by destroying its neovessels. 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), 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). 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.
Référence
Int J Nanomedicine. 2017 ;12:7075-7088