Multifunctional ultrasmall nanoplatforms for vascular-targeted interstitial photodynamic therapy of brain tumors guided by real-time MRI

Denise Bechet (1) , Florent Auger (2, 3) , Pierre Couleaud (4) , Eric Marty (5) , Laura Ravasi (2, 3) , Nicolas Durieux (2, 3) , Corinne Bonnet (6) , François Plénat (1, 6) , Céline Frochot (4) , Serge R. Mordon (7) , Olivier Tillement (8) , Régis Vanderesse (9) , François Lux (8) , Pascal Perriat (8) , François Guillemin (1) , Muriel Barberi-Heyob (1)

1 CRAN - Centre de Recherche en Automatique de Nancy
2 IMPRT - Institut de médecine predictive et de recherche thérapeutique
3 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
4 LRGP - Laboratoire Réactions et Génie des Procédés
5 Sans affiliation
6 CHRU Nancy - Centre Hospitalier Régional Universitaire de Nancy
7 OncoThAI - Thérapies Assistées par Lasers et Immunothérapies pour l'Oncologie - U 1189
8 ILM - Institut Lumière Matière [Villeurbanne]
9 LCPM - Laboratoire de Chimie Physique Macromoléculaire

Photodynamic therapy (PDT) for brain tumors appears to be complementary to conventional treatments. A number of studies show the major role of the vascular effect in the tumor eradication by PDT. For interstitial PDT (iPDT) of brain tumors guided by real-time imaging, multifunctional nanoparticles consisting of a surface-localized tumor vasculature targeting neuropilin-1 (NRP-1) peptide and encapsulated photosensitizer and magnetic resonance imaging (MRI) contrast agents, have been designed. Nanoplatforms confer photosensitivity to cells and demonstrate a molecular affinity to NRP-1. Intravenous injection into rats bearing intracranial glioma exhibited a dynamic contrast-enhanced MRI for angiogenic endothelial cells lining the neovessels mainly located in the peripheral tumor. By using MRI completed by NRP-1 protein expression of the tumor and brain adjacent to tumor tissues, we checked the selectivity of the nanoparticles. This study represents the first in vivo proof of concept of closed-head iPDT guided by real-time MRI using targeted ultrasmall nanoplatforms. From the clinical editor: The authors constructed tumor vascular peptide targeting multifunctional silica-based nanoparticles, with encapsulated gadolinium oxide as MRI contrast agent and chlorin as a photosensitizer, as a proof of concept novel treatment for glioblastoma in an animal model.

Mots clés: iPDT; brain tumor; real-time MRI; targeting; multifunctional nanoplateforms

Domaines: Cancer

Denise Bechet, Florent Auger, Pierre Couleaud, Eric Marty, Laura Ravasi, et al.. Multifunctional ultrasmall nanoplatforms for vascular-targeted interstitial photodynamic therapy of brain tumors guided by real-time MRI. Nanomedicine, 2015, 11 (3), pp.657-670. ⟨10.1016/j.nano.2014.12.007⟩. ⟨hal-01096721⟩