Long-Term in Vivo Clearance of Gadolinium-Based AGuIX Nanoparticles and Their Biocompatibility after Systemic Injection

Lucie Sancey (1) , Shady Kotb (1) , Charles Truillet (1) , F. Appaix (2) , Arthur Marais (1) , E. Thomas (1) , B. van Der Sanden (2) , Klein J.-P. (3) , B. Laurent (3) , M. Cottier (3) , Rodolphe Antoine (1) , P. Dugourd (1) , Gérard Panczer (1) , François Lux (1) , P. Perriat (4) , Vincent Motto-Ros (1) , Olivier Tillement (1)

1 ILM - Institut Lumière Matière [Villeurbanne]
2 GIN - [GIN] Grenoble Institut des Neurosciences
3 LINA-ENSMSE - Laboratoire Interdisciplinaire d'Etude des Nanoparticules Aérosolisées
4 MATEIS - Matériaux, ingénierie et science [Villeurbanne]

We previously reported the synthesis of gadolinium-based nanoparticles (NPs) denoted AGuIX (activation and guiding of irradiation by X-ray) NPs and demonstrated their potential as an MRI contrast agent and their efficacy as radiosensitizing particles during X-ray cancer treatment. Here we focus on the elimination kinetics of AGuIX NPs from the subcellular to whole-organ scale using original and complementary methods such as laser-induced breakdown spectroscopy (LIBS), intravital two-photon microscopy, inductively coupled plasma optical emission spectrometry (ICP-OES), transmission electron microscopy (TEM), and electrospray ionization mass spectrometry (ESI-MS). This combination of techniques allows the exact mechanism of AGuIX NPs elimination to be elucidated, including their retention in proximal tubules and their excretion as degraded or native NPs. Finally, we demonstrated that systemic AGuIX NP administration induced moderate and transient effects on renal function. These results provide useful and promising preclinical information concerning the safety of theranostic AGuIX NPs.

Domaines: Cancer

Lucie Sancey, Shady Kotb, Charles Truillet, F. Appaix, Arthur Marais, et al.. Long-Term in Vivo Clearance of Gadolinium-Based AGuIX Nanoparticles and Their Biocompatibility after Systemic Injection. ACS Nano, 2015, 9 (3), pp.2477-2488. ⟨10.1021/acsnano.5b00552⟩. ⟨hal-01207383⟩