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

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

Eloïse Thomas,1 Ludovic Colombeau,2 Mickaël Gries,3,4 Thibaut Peterlini,3,4 Clélia Mathieu,1 Noémie Thomas,3,4 Cédric Boura,3,4 Céline Frochot,2 Régis Vanderesse,5 François Lux,1 Muriel Barberi-Heyob,3,4 Olivier Till...

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Autores principales: 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
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2017
Materias:
Nanoparticles
PDT
Vascular targeting strategy
Glioblastoma
NRP-1
Peptide ligand.
Medicine (General)
R5-920
Acceso en línea:https://doaj.org/article/5846f10bd96e414d9b28daf215808f16
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spelling oai:doaj.org-article:5846f10bd96e414d9b28daf215808f162021-12-02T02:21:11ZUltrasmall AGuIX theranostic nanoparticles for vascular-targeted interstitial photodynamic therapy of glioblastoma1178-2013https://doaj.org/article/5846f10bd96e414d9b28daf215808f162017-09-01T00:00:00Zhttps://www.dovepress.com/ultrasmall-aguix-theranostic-nanoparticles-for-vascular-targeted-inter-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Eloïse Thomas,1 Ludovic Colombeau,2 Mickaël Gries,3,4 Thibaut Peterlini,3,4 Clélia Mathieu,1 Noémie Thomas,3,4 Cédric Boura,3,4 Céline Frochot,2 Régis Vanderesse,5 François Lux,1 Muriel Barberi-Heyob,3,4 Olivier Tillement1 1Université Lyon, Université Claude Bernard Lyon 1, Centre National de la Recherche Scientifique (CNRS), Institut Lumière Matière, Lyon, 2Laboratoire Réactions et Génie des Procédés, Université de Lorraine-CNRS, Nancy, 3Université de Lorraine, Research Center for Automatic Control of Nancy (CRAN), 4CNRS, CRAN, Vandœuvre-lès-Nancy, 5Laboratoire de Chimie Physique Macromoléculaire, Université de Lorraine-CNRS, Nancy, France Abstract: 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, MRIThomas EColombeau LGries MPeterlini TMathieu CThomas NBoura CFrochot CVanderesse RLux FBarberi-Heyob MTillement ODove Medical PressarticleNanoparticlesPDTVascular targeting strategyGlioblastomaNRP-1Peptide ligand.Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 7075-7088 (2017)
institution DOAJ
collection DOAJ
language EN
topic Nanoparticles
PDT
Vascular targeting strategy
Glioblastoma
NRP-1
Peptide ligand.
Medicine (General)
R5-920
spellingShingle Nanoparticles
PDT
Vascular targeting strategy
Glioblastoma
NRP-1
Peptide ligand.
Medicine (General)
R5-920
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
Ultrasmall AGuIX theranostic nanoparticles for vascular-targeted interstitial photodynamic therapy of glioblastoma
description Eloïse Thomas,1 Ludovic Colombeau,2 Mickaël Gries,3,4 Thibaut Peterlini,3,4 Clélia Mathieu,1 Noémie Thomas,3,4 Cédric Boura,3,4 Céline Frochot,2 Régis Vanderesse,5 François Lux,1 Muriel Barberi-Heyob,3,4 Olivier Tillement1 1Université Lyon, Université Claude Bernard Lyon 1, Centre National de la Recherche Scientifique (CNRS), Institut Lumière Matière, Lyon, 2Laboratoire Réactions et Génie des Procédés, Université de Lorraine-CNRS, Nancy, 3Université de Lorraine, Research Center for Automatic Control of Nancy (CRAN), 4CNRS, CRAN, Vandœuvre-lès-Nancy, 5Laboratoire de Chimie Physique Macromoléculaire, Université de Lorraine-CNRS, Nancy, France Abstract: 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
format article
author 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
author_facet 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
author_sort Thomas E
title Ultrasmall AGuIX theranostic nanoparticles for vascular-targeted interstitial photodynamic therapy of glioblastoma
title_short Ultrasmall AGuIX theranostic nanoparticles for vascular-targeted interstitial photodynamic therapy of glioblastoma
title_full Ultrasmall AGuIX theranostic nanoparticles for vascular-targeted interstitial photodynamic therapy of glioblastoma
title_fullStr Ultrasmall AGuIX theranostic nanoparticles for vascular-targeted interstitial photodynamic therapy of glioblastoma
title_full_unstemmed Ultrasmall AGuIX theranostic nanoparticles for vascular-targeted interstitial photodynamic therapy of glioblastoma
title_sort ultrasmall aguix theranostic nanoparticles for vascular-targeted interstitial photodynamic therapy of glioblastoma
publisher Dove Medical Press
publishDate 2017
url https://doaj.org/article/5846f10bd96e414d9b28daf215808f16
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