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ACS Nano. 2015 Mar 24;9(3):2477-88. doi: 10.1021/acsnano.5b00552. Epub 2015 Feb 26.

Long-term in vivo clearance of gadolinium-based AGuIX nanoparticles and their biocompatibility after systemic injection.

Author information

1
†Institut lumière matière, UMR5306, Université Claude Bernard Lyon1-CNRS, Université de Lyon 69622 Villeurbanne cedex, France.
2
‡GIN INSERM U836 UJF, Grenoble, 38706, France.
3
§LINA EA 4624-Laboratoire Interdisciplinaire d'étude des Nanoparticules Aérosolisées, Saint Etienne, 42023, France.
4
∥MATEIS, UMR 5510 INSA Lyon-CNRS, INSA Lyon, 69621 Villeurbanne, France.

Abstract

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.

KEYWORDS:

gadolinium; laser-induced breakdown spectroscopy; nanoparticle; renal function; theranostic; toxicity; two-photon microscopy

PMID:
25703068
DOI:
10.1021/acsnano.5b00552
[Indexed for MEDLINE]

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