Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

Version 1 : Received: 7 February 2020 / Approved: 9 February 2020 / Online: 9 February 2020 (17:37:11 CET)

A peer-reviewed article of this Preprint also exists.

Claveau, S.; Nehlig, É.; Garcia-Argote, S.; Feuillastre, S.; Pieters, G.; Girard, H.A.; Arnault, J.-C.; Treussart, F.; Bertrand, J.-R. Delivery of siRNA to Ewing Sarcoma Tumor Xenografted on Mice, Using Hydrogenated Detonation Nanodiamonds: Treatment Efficacy and Tissue Distribution. Nanomaterials 2020, 10, 553. Claveau, S.; Nehlig, É.; Garcia-Argote, S.; Feuillastre, S.; Pieters, G.; Girard, H.A.; Arnault, J.-C.; Treussart, F.; Bertrand, J.-R. Delivery of siRNA to Ewing Sarcoma Tumor Xenografted on Mice, Using Hydrogenated Detonation Nanodiamonds: Treatment Efficacy and Tissue Distribution. Nanomaterials 2020, 10, 553.

Journal reference: Nanomaterials 2020, 10, 553
DOI: 10.3390/nano10030553

Abstract

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 adult due in the vast majority to the EWS-Fli1 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 EWS-Fli1 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.

Subject Areas

nanodiamond; tritium; biodistribution; Ewing sarcoma; drug delivery; siRNA; nanomedicine

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