Tuning ultrasmall theranostic nanoparticles for MRI contrast and radiation dose amplification
Needa Brown
(1, 2)
,
Paul Rocchi
(3, 4)
,
Léna Carmès
(3, 4)
,
Romy Guthier
(1, 5)
,
Meghna Iyer
(1, 2)
,
Léa Seban
(1)
,
Toby Morris
(1, 5)
,
Stephanie Bennett
(1)
,
Michael Lavelle
(1, 5)
,
Johany Penailillo
(6, 7)
,
Ruben Carrasco
(6, 7, 8)
,
Chris Williams
(1)
,
Elizabeth Huynh
(1)
,
Zhaohui Han
(1)
,
Evangelia Kaza
(1)
,
Tristan Doussineau
(3)
,
Sneh M Toprani
(9)
,
Xingping Qin
(9, 6, 7)
,
Zachary D Nagel
(9)
,
Kristopher A Sarosiek
(9, 6, 7)
,
Agnès Hagège
(10)
,
Sandrine Dufort
(11)
,
Guillaume Bort
(4)
,
François Lux
(4, 12)
,
Olivier Tillement
(4)
,
Ross Berbeco
(1)
1
Brigham and Women’s Hospital [Boston, MA]
2 Northeastern University [Boston]
3 NHTheraguix [Crolles]
4 iLM - FENNEC - iLM - Formation, élaboration de nanomatériaux et cristaux
5 Department of Physics and Applied Physics [Lowell]
6 HMS - Harvard Medical School [Boston]
7 Dana-Farber Cancer Institute [Boston]
8 Brigham and Women's Hospital [Boston]
9 Harvard T.H. Chan School of Public Health
10 TechSep - ISA-Separative Methods - Techniques séparatives
11 NH TherAguix SA [Meylan]
12 IUF - Institut universitaire de France
2 Northeastern University [Boston]
3 NHTheraguix [Crolles]
4 iLM - FENNEC - iLM - Formation, élaboration de nanomatériaux et cristaux
5 Department of Physics and Applied Physics [Lowell]
6 HMS - Harvard Medical School [Boston]
7 Dana-Farber Cancer Institute [Boston]
8 Brigham and Women's Hospital [Boston]
9 Harvard T.H. Chan School of Public Health
10 TechSep - ISA-Separative Methods - Techniques séparatives
11 NH TherAguix SA [Meylan]
12 IUF - Institut universitaire de France
Needa Brown
- Fonction : Auteur
- PersonId : 1288723
Agnès Hagège
- Fonction : Auteur
- PersonId : 987963
- IdHAL : agneshagege
- ORCID : 0000-0002-9246-929X
Guillaume Bort
- Fonction : Auteur
- PersonId : 184123
- IdHAL : guillaume-bort
- ORCID : 0000-0001-9248-955X
- IdRef : 181586665
Résumé
Background: The introduction of magnetic resonance (MR)-guided radiation treatment planning has opened a new space for theranostic nanoparticles to reduce acute toxicity while improving local control. In this work, second-generation AGuIX ® nanoparticles (AGuIX-Bi) are synthesized and validated. AGuIX-Bi are shown to maintain MR positive contrast while further amplifying the radiation dose by the replacement of some Gd 3+ cations with higher Z Bi 3+. These next-generation nanoparticles are based on the AGuIX ® platform, which is currently being evaluated in multiple Phase II clinical trials in combination with radiotherapy. Methods: In this clinically scalable methodology, AGuIX ® is used as an initial chelation platform to exchange Gd 3+ for Bi 3+. AGuIX-Bi nanoparticles are synthesized with three ratios of Gd/Bi, each maintaining MR contrast while further amplifying radiation dose relative to Bi 3+. Safety, efficacy, and theranostic potential of the nanoparticles were evaluated in vitro and in vivo in a human non-small cell lung cancer model. Results: We demonstrated that increasing Bi 3+ in the nanoparticles is associated with more DNA damage and improves in vivo efficacy with a statistically significant delay in tumor growth and 33% complete regression for the largest Bi/Gd ratio tested. The addition of Bi 3+ by our synthetic method leads to nanoparticles that present slightly altered pharmacokinetics and lengthening of the period of high tumor accumulation with no observed evidence of toxicity. Conclusions: We confirmed the safety and enhanced efficacy of AGuIX-Bi with radiation therapy at the selected ratio of 30Gd/70Bi. These results provide crucial evidence towards patient translation.
Format du dépôt | Fichier |
---|---|
Type de dépôt | Article dans une revue |
Titre |
en
Tuning ultrasmall theranostic nanoparticles for MRI contrast and radiation dose amplification
|
Résumé |
en
Background: The introduction of magnetic resonance (MR)-guided radiation treatment planning has opened a new space for theranostic nanoparticles to reduce acute toxicity while improving local control. In this work, second-generation AGuIX ® nanoparticles (AGuIX-Bi) are synthesized and validated. AGuIX-Bi are shown to maintain MR positive contrast while further amplifying the radiation dose by the replacement of some Gd 3+ cations with higher Z Bi 3+. These next-generation nanoparticles are based on the AGuIX ® platform, which is currently being evaluated in multiple Phase II clinical trials in combination with radiotherapy. Methods: In this clinically scalable methodology, AGuIX ® is used as an initial chelation platform to exchange Gd 3+ for Bi 3+. AGuIX-Bi nanoparticles are synthesized with three ratios of Gd/Bi, each maintaining MR contrast while further amplifying radiation dose relative to Bi 3+. Safety, efficacy, and theranostic potential of the nanoparticles were evaluated in vitro and in vivo in a human non-small cell lung cancer model. Results: We demonstrated that increasing Bi 3+ in the nanoparticles is associated with more DNA damage and improves in vivo efficacy with a statistically significant delay in tumor growth and 33% complete regression for the largest Bi/Gd ratio tested. The addition of Bi 3+ by our synthetic method leads to nanoparticles that present slightly altered pharmacokinetics and lengthening of the period of high tumor accumulation with no observed evidence of toxicity. Conclusions: We confirmed the safety and enhanced efficacy of AGuIX-Bi with radiation therapy at the selected ratio of 30Gd/70Bi. These results provide crucial evidence towards patient translation.
|
Auteur(s) |
Needa Brown
1, 2
, Paul Rocchi
3, 4
, Léna Carmès
3, 4
, Romy Guthier
1, 5
, Meghna Iyer
1, 2
, Léa Seban
1
, Toby Morris
1, 5
, Stephanie Bennett
1
, Michael Lavelle
1, 5
, Johany Penailillo
6, 7
, Ruben Carrasco
6, 7, 8
, Chris Williams
1
, Elizabeth Huynh
1
, Zhaohui Han
1
, Evangelia Kaza
1
, Tristan Doussineau
3
, Sneh M Toprani
9
, Xingping Qin
9, 6, 7
, Zachary D Nagel
9
, Kristopher A Sarosiek
9, 6, 7
, Agnès Hagège
10
, Sandrine Dufort
11
, Guillaume Bort
4
, François Lux
4, 12
, Olivier Tillement
4
, Ross Berbeco
1
1
Brigham and Women’s Hospital [Boston, MA]
( 1095068 )
- 75 Francis Street, Boston MA 02115
- États-Unis
2
Northeastern University [Boston]
( 29479 )
- 360 Huntington Ave., Boston, Massachusetts 02115
- États-Unis
3
NHTheraguix [Crolles]
( 578746 )
- France
4
iLM - FENNEC -
iLM - Formation, élaboration de nanomatériaux et cristaux
( 394718 )
- France
5
Department of Physics and Applied Physics [Lowell]
( 126528 )
- Lowell, MA 01854
- États-Unis
6
HMS -
Harvard Medical School [Boston]
( 130467 )
- 25 Shattuck Street Boston, MA 02115
- États-Unis
7
Dana-Farber Cancer Institute [Boston]
( 142307 )
- 450 Brookline Ave.
Boston, MA 02215
- États-Unis
8
Brigham and Women's Hospital [Boston]
( 300206 )
- 75 Francis St, Boston, MA 02115
- États-Unis
9
Harvard T.H. Chan School of Public Health
( 458379 )
- 677 Huntington Avenue, Boston, MA 02115
- États-Unis
10
TechSep -
ISA-Separative Methods - Techniques séparatives
( 426116 )
- Institut des Sciences Analytiques (ISA)
UMR 5280
05, rue de la DOUA
69100 Villeurbanne (France)
- France
11
NH TherAguix SA [Meylan]
( 1040395 )
- 29 chemin du Vieux Chêne, 38240 Meylan
- France
12
IUF -
Institut universitaire de France
( 56663 )
- Maison des Universités 103 Boulevard Saint-Michel 75005 Paris
- France
|
Langue du document |
Anglais
|
Nom de la revue |
|
Date de publication |
2023
|
Volume |
13
|
Page/Identifiant |
4711 - 4729
|
Vulgarisation |
Non
|
Comité de lecture |
Oui
|
Audience |
Internationale
|
Domaine(s) |
|
Mots-clés |
en
nanoparticle bismuth theranostics magnetic resonance radiation therapy, nanoparticle, bismuth, theranostics, magnetic resonance, radiation therapy
|
arXiv Id | 2310.01179 |
DOI | 10.7150/thno.85663 |
Origine :
Fichiers produits par l'(les) auteur(s)
Loading...