Delivery of siRNA to Ewing Sarcoma Tumor Xenografted on Mice, Using Hydrogenated Detonation Nanodiamonds: Treatment Efficacy and Tissue Distribution

Nanodiamonds of detonation origin are promising delivery agents of anti-cancer therapeutic compounds in a whole organism like mouse, owing to their versatile surface chemistry and ultra-small 5 nm average primary size compatible with natural elimination routes. However, to date, little is known abou...

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Main Authors: Sandra Claveau, Émilie Nehlig, Sébastien Garcia-Argote, Sophie Feuillastre, Grégory Pieters, Hugues A. Girard, Jean-Charles Arnault, François Treussart, Jean-Rémi Bertrand
Format: Article
Language:English
Published: MDPI AG 2020-03-01
Series:Nanomaterials
Subjects:
Online Access:https://www.mdpi.com/2079-4991/10/3/553
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author Sandra Claveau
Émilie Nehlig
Sébastien Garcia-Argote
Sophie Feuillastre
Grégory Pieters
Hugues A. Girard
Jean-Charles Arnault
François Treussart
Jean-Rémi Bertrand
author_facet Sandra Claveau
Émilie Nehlig
Sébastien Garcia-Argote
Sophie Feuillastre
Grégory Pieters
Hugues A. Girard
Jean-Charles Arnault
François Treussart
Jean-Rémi Bertrand
author_sort Sandra Claveau
collection DOAJ
description Nanodiamonds of detonation origin are promising delivery agents of anti-cancer therapeutic compounds in a whole organism like mouse, owing to their versatile surface chemistry and ultra-small 5 nm average primary size compatible with natural elimination routes. However, to date, little is known about tissue distribution, elimination pathways and efficacy of nanodiamonds-based therapy in mice. In this report, we studied the capacity of cationic hydrogenated detonation nanodiamonds to carry active small interfering RNA (siRNA) in a mice model of Ewing sarcoma, a bone cancer of young adults due in the vast majority to the <i>EWS-FLI1</i> junction oncogene. Replacing hydrogen gas by its radioactive analog tritium gas led to the formation of labeled nanodiamonds and allowed us to investigate their distribution throughout mouse organs and their excretion in urine and feces. We also demonstrated that siRNA directed against <i>EWS-FLI1</i> inhibited this oncogene expression in tumor xenografted on mice. This work is a significant step to establish cationic hydrogenated detonation nanodiamond as an effective agent for in vivo delivery of active siRNA.
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spelling doaj.art-acb07f08dcc64ff596b8d1e412979a252022-12-22T03:42:30ZengMDPI AGNanomaterials2079-49912020-03-0110355310.3390/nano10030553nano10030553Delivery of siRNA to Ewing Sarcoma Tumor Xenografted on Mice, Using Hydrogenated Detonation Nanodiamonds: Treatment Efficacy and Tissue DistributionSandra Claveau0Émilie Nehlig1Sébastien Garcia-Argote2Sophie Feuillastre3Grégory Pieters4Hugues A. Girard5Jean-Charles Arnault6François Treussart7Jean-Rémi Bertrand8LuMIn, CNRS, ENS Paris-Saclay, CentraleSupélec, Université Paris-Saclay, 91405 Orsay, FranceSCBM, Institut Joliot, CEA, Université Paris-Saclay, 91191 Gif-sur-Yvette, FranceSCBM, Institut Joliot, CEA, Université Paris-Saclay, 91191 Gif-sur-Yvette, FranceSCBM, Institut Joliot, CEA, Université Paris-Saclay, 91191 Gif-sur-Yvette, FranceSCBM, Institut Joliot, CEA, Université Paris-Saclay, 91191 Gif-sur-Yvette, FranceDiamond Sensors Laboratory, Institut LIST, CEA, Université Paris-Saclay, 91191 Gif-sur-Yvette, FranceDiamond Sensors Laboratory, Institut LIST, CEA, Université Paris-Saclay, 91191 Gif-sur-Yvette, FranceLuMIn, CNRS, ENS Paris-Saclay, CentraleSupélec, Université Paris-Saclay, 91405 Orsay, FranceVectorologie et Thérapeutiques Anticancéreuses, CNRS, Institut Gustave Roussy, Université Paris-Saclay, 94805 Villejuif, FranceNanodiamonds of detonation origin are promising delivery agents of anti-cancer therapeutic compounds in a whole organism like mouse, owing to their versatile surface chemistry and ultra-small 5 nm average primary size compatible with natural elimination routes. However, to date, little is known about tissue distribution, elimination pathways and efficacy of nanodiamonds-based therapy in mice. In this report, we studied the capacity of cationic hydrogenated detonation nanodiamonds to carry active small interfering RNA (siRNA) in a mice model of Ewing sarcoma, a bone cancer of young adults due in the vast majority to the <i>EWS-FLI1</i> junction oncogene. Replacing hydrogen gas by its radioactive analog tritium gas led to the formation of labeled nanodiamonds and allowed us to investigate their distribution throughout mouse organs and their excretion in urine and feces. We also demonstrated that siRNA directed against <i>EWS-FLI1</i> inhibited this oncogene expression in tumor xenografted on mice. This work is a significant step to establish cationic hydrogenated detonation nanodiamond as an effective agent for in vivo delivery of active siRNA.https://www.mdpi.com/2079-4991/10/3/553nanodiamondtritiumbiodistributionewing sarcomadrug deliverysirnananomedicine
spellingShingle Sandra Claveau
Émilie Nehlig
Sébastien Garcia-Argote
Sophie Feuillastre
Grégory Pieters
Hugues A. Girard
Jean-Charles Arnault
François Treussart
Jean-Rémi Bertrand
Delivery of siRNA to Ewing Sarcoma Tumor Xenografted on Mice, Using Hydrogenated Detonation Nanodiamonds: Treatment Efficacy and Tissue Distribution
Nanomaterials
nanodiamond
tritium
biodistribution
ewing sarcoma
drug delivery
sirna
nanomedicine
title Delivery of siRNA to Ewing Sarcoma Tumor Xenografted on Mice, Using Hydrogenated Detonation Nanodiamonds: Treatment Efficacy and Tissue Distribution
title_full Delivery of siRNA to Ewing Sarcoma Tumor Xenografted on Mice, Using Hydrogenated Detonation Nanodiamonds: Treatment Efficacy and Tissue Distribution
title_fullStr Delivery of siRNA to Ewing Sarcoma Tumor Xenografted on Mice, Using Hydrogenated Detonation Nanodiamonds: Treatment Efficacy and Tissue Distribution
title_full_unstemmed Delivery of siRNA to Ewing Sarcoma Tumor Xenografted on Mice, Using Hydrogenated Detonation Nanodiamonds: Treatment Efficacy and Tissue Distribution
title_short Delivery of siRNA to Ewing Sarcoma Tumor Xenografted on Mice, Using Hydrogenated Detonation Nanodiamonds: Treatment Efficacy and Tissue Distribution
title_sort delivery of sirna to ewing sarcoma tumor xenografted on mice using hydrogenated detonation nanodiamonds treatment efficacy and tissue distribution
topic nanodiamond
tritium
biodistribution
ewing sarcoma
drug delivery
sirna
nanomedicine
url https://www.mdpi.com/2079-4991/10/3/553
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