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

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 designe...

Full description

Saved in:
Bibliographic Details
Published in:International Journal of Nanomedicine 2017, Vol.12, p.7075
Main Authors: Thomas, Eloise, Colombeau, Ludovic, Gries, Mickael, Peterlini, Thibaut, Mathieu, Clelia, Thomas, Noemie, Boura, Cedric, Frochot, Celine, Vanderesse, Regis, Lux, Frangois, Barberi-Heyob, Muriel, Tillement, Olivier
Format: Report
Language:English
Subjects:
Brain tumors
Care and treatment
Glioblastomas
Magnetic resonance imaging
Photochemotherapy
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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. Keywords: nanoparticles, PDT, vascular targeting strategy, brain tumor, NRP-1, peptide ligand, MRI
ISSN:1178-2013
DOI:10.2147/IJN.S141559