Ultrasmall theranostic gadolinium-based nanoparticles improve high-grade rat glioma survival
Sandrine Dufort
(1)
,
Geoffrey Appelboom
(2)
,
Camille Verry
(3, 4)
,
Emmanuel L. Barbier
(4)
,
François Lux
(5)
,
Elke Bräuer-Krisch
(6)
,
Lucie Sancey
(5, 7)
,
Steven D Chang
(2)
,
Michael Zhang
(2)
,
Stéphane Roux
(8, 9)
,
Olivier Tillement
(5)
,
Géraldine Le Duc
(6)
1
NanoH-sas
2 Stanford University
3 Service de radiothérapie- CHU de Grenoble
4 GIN - [GIN] Grenoble Institut des Neurosciences
5 iLM - FENNEC - iLM - Formation, élaboration de nanomatériaux et cristaux
6 ESRF - European Synchrotron Radiation Facility
7 IAB - Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble)
8 Phys-ENS - Laboratoire de Physique de l'ENS Lyon
9 UTINAM - Univers, Théorie, Interfaces, Nanostructures, Atmosphère et environnement, Molécules (UMR 6213)
2 Stanford University
3 Service de radiothérapie- CHU de Grenoble
4 GIN - [GIN] Grenoble Institut des Neurosciences
5 iLM - FENNEC - iLM - Formation, élaboration de nanomatériaux et cristaux
6 ESRF - European Synchrotron Radiation Facility
7 IAB - Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble)
8 Phys-ENS - Laboratoire de Physique de l'ENS Lyon
9 UTINAM - Univers, Théorie, Interfaces, Nanostructures, Atmosphère et environnement, Molécules (UMR 6213)
Camille Verry
- Fonction : Auteur
- PersonId : 765022
- ORCID : 0000-0002-9362-7624
Emmanuel L. Barbier
- Fonction : Auteur
- PersonId : 745767
- IdHAL : emmanuel-barbier
- ORCID : 0000-0002-4952-1240
- IdRef : 120242079
Lucie Sancey
- Fonction : Auteur
- PersonId : 179893
- IdHAL : lucie-sancey
- ORCID : 0000-0002-0084-3775
- IdRef : 110676858
Stéphane Roux
- Fonction : Auteur
- PersonId : 1171786
- IdHAL : stephane-roux6249
- ORCID : 0000-0002-5198-1916
Olivier Tillement
- Fonction : Auteur
- PersonId : 938819
- ORCID : 0000-0001-7166-6537
- IdRef : 085752002
Résumé
We formulated an ultra-small, gadolinium-based nanoparticle (AGuIX) with theranostic properties to simultaneously enhance MRI tumor delineation and radiosensitization in a glioma model. The 9L glioma cells were orthotopically implanted in 10-week-old Fischer rats. The intra-tumoral accumulation of AGuIX was quantified using MRI T1-maps. Rats randomized to intervention cohorts were subsequently treated with daily temozolomide for five consecutive days before radiotherapy treatment. Collectively, a series of 32 rats were divided into untreated (n = 7), temozolomide-only (n = 7), temozolomide and MRT (n = 9), AGuIX and MRT (n = 7), and triple therapy (temozolomide, AGuIX NPs, and MRT; n = 9) cohorts. AGuIX nanoparticles achieved a maximum intra-tumoral concentration (expressed as concentration of Gd3+) at 1 h after intravenous injection, reaching a mean of 227.9 ± 60 lM. This was compared to concentrations of 10.5 ± 9.2 lM and 62.9 ± 24.7 lM in the contralateral hemisphere and cheek, respectively. There was a slower washout in the intra-tumor region, with sustained tumor-to-contralateral ratio of AGuIX, up to 14-fold, for each time point. The combination of AGuIX or temozolomide with MRT improved the median survival time (40 days) compared to the MeST of control rats (25 days) (p < 0.002). There was a trend towards further increased survival when the three treatments were combined (MeST of 46 days). This study demonstrated the selective accumulation of AGuIX in high grade glioma, as well as the potential survival benefits when combined with chemoradiation.
Format du dépôt | Fichier |
---|---|
Type de dépôt | Article dans une revue |
Titre |
en
Ultrasmall theranostic gadolinium-based nanoparticles improve high-grade rat glioma survival
|
Résumé |
en
We formulated an ultra-small, gadolinium-based nanoparticle (AGuIX) with theranostic properties to simultaneously enhance MRI tumor delineation and radiosensitization in a glioma model. The 9L glioma cells were orthotopically implanted in 10-week-old Fischer rats. The intra-tumoral accumulation of AGuIX was quantified using MRI T1-maps. Rats randomized to intervention cohorts were subsequently treated with daily temozolomide for five consecutive days before radiotherapy treatment. Collectively, a series of 32 rats were divided into untreated (n = 7), temozolomide-only (n = 7), temozolomide and MRT (n = 9), AGuIX and MRT (n = 7), and triple therapy (temozolomide, AGuIX NPs, and MRT; n = 9) cohorts. AGuIX nanoparticles achieved a maximum intra-tumoral concentration (expressed as concentration of Gd3+) at 1 h after intravenous injection, reaching a mean of 227.9 ± 60 lM. This was compared to concentrations of 10.5 ± 9.2 lM and 62.9 ± 24.7 lM in the contralateral hemisphere and cheek, respectively. There was a slower washout in the intra-tumor region, with sustained tumor-to-contralateral ratio of AGuIX, up to 14-fold, for each time point. The combination of AGuIX or temozolomide with MRT improved the median survival time (40 days) compared to the MeST of control rats (25 days) (p < 0.002). There was a trend towards further increased survival when the three treatments were combined (MeST of 46 days). This study demonstrated the selective accumulation of AGuIX in high grade glioma, as well as the potential survival benefits when combined with chemoradiation.
|
Auteur(s) |
Sandrine Dufort
1
, Geoffrey Appelboom
2
, Camille Verry
3, 4
, Emmanuel L. Barbier
4
, François Lux
5
, Elke Bräuer-Krisch
6
, Lucie Sancey
5, 7
, Steven D Chang
2
, Michael Zhang
2
, Stéphane Roux
8, 9
, Olivier Tillement
5
, Géraldine Le Duc
6
1
NanoH-sas
( 70913 )
- 23 rue Royal 69001 Lyon
- France
2
Stanford University
( 73500 )
- 450 Serra Mall, Stanford, CA 94305-2004
- États-Unis
3
Service de radiothérapie- CHU de Grenoble
( 107476 )
- B.P. 217 38043 Grenoble cedex
- France
4
GIN -
[GIN] Grenoble Institut des Neurosciences
( 408885 )
- Site Santé - Bâtiment Edmond J. Safra - Chemin Fortuné Ferrini 38706 La Tronche Cedex
- France
5
iLM - FENNEC -
iLM - Formation, élaboration de nanomatériaux et cristaux
( 394718 )
- France
6
ESRF -
European Synchrotron Radiation Facility
( 2568 )
- 6 rue Jules Horowitz BP220 38043 GRENOBLE CEDEX
- France
7
IAB -
Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble)
( 472784 )
- Institut pour l'Avancée des Biosciences
Centre de Recherche UGA / Inserm U 1209 / CNRS UMR 5309
Site Santé - Allée des Alpes
38700 La Tronche
- France
8
Phys-ENS -
Laboratoire de Physique de l'ENS Lyon
( 13 )
- 46 allée d'Italie 69007 Lyon
- France
9
UTINAM -
Univers, Théorie, Interfaces, Nanostructures, Atmosphère et environnement, Molécules (UMR 6213)
( 85871 )
- 16, route de Gray 25030 BESANCON CEDEX France
- France
|
Comité de lecture |
Oui
|
Audience |
Internationale
|
Date de publication |
2019-09-01
|
Date de publication électronique |
2019-07-04
|
Volume |
67
|
Page/Identifiant |
215-219
|
Langue du document |
Anglais
|
Nom de la revue |
|
Vulgarisation |
Non
|
Domaine(s) |
|
Projet(s) ANR |
|
Mots-clés |
en
Radiosensitizers, Theranostic, Nanoparticles, Glioblastoma, Temozolomide, Chemoradiation
|
DOI | 10.1016/j.jocn.2019.05.065 |
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