Journal
ACS NANO
Volume 9, Issue 3, Pages 2477-2488Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.5b00552
Keywords
nanoparticle; gadolinium; theranostic; two-photon microscopy; laser-induced breakdown spectroscopy; renal function; toxicity
Categories
Funding
- LABEX iMUST of Lyon 1 University within the programs Investissements d'Avenir [ANR-10-LABX-0064, ANR-11IDEX-0007]
- PRIMES of Lyon 1 University within the programs Investissements d'Avenir [ANR-11-LABX-0063, ANR-11IDEX-0063]
- ANR Multimage [ANR-12-RPIB-0010]
- Lyon Science Transfert
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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.
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