Preferential tumour accumulation of gold nanoparticles, visualised by magnetic resonance imaging: Radiosensitisation studies in vivo and in vitro

• Published in: International journal of radiation biology Vol. 86; no. 8; pp. 692 - 700
• Main Authors: Hébert, Etienne M., Debouttière, Pierre-Jean, Lepage, Martin, Sanche, Léon, Hunting, Darel J.
• Format: Journal Article
• Language: English
• Published: England Informa UK Ltd 01.08.2010; Taylor & Francis
• Subjects: Animals; Cell Line, Tumor; chemotherapeutic effect; Female; Gadolinium DTPA - pharmacokinetics; Gadolinium DTPA - pharmacology; Gold - pharmacokinetics; Gold - pharmacology; gold nanoparticles; Kaplan-Meier; low energy electrons; Magnetic Resonance Imaging - methods; Mammary Neoplasms, Experimental - metabolism; Mammary Neoplasms, Experimental - mortality; Mammary Neoplasms, Experimental - radiotherapy; Mice; Mice, Inbred BALB C; MRI contrast agents; Nanoparticles; Radiation-Sensitizing Agents - pharmacology; radiosensitisers
• ISSN: 0955-3002; 1362-3095
• DOI: 10.3109/09553001003746067

Purpose: To investigate the radiosensitisation of gold nanoparticles (GNP) with an average diameter of 5 nm coated with the gadolinium chelating agent dithiolated diethylenetriaminepentaacetic gadolinium (Au@DTDTPA:Gd) in vitro and in mice bearing tumours (MC7-L1). Materials and methods: In vivo, the gadolinium chelate coating allows one to perform real-time Magnetic Resonance Imaging (MRI) pharmacokinetic analysis during intravenous infusion. Experiments were performed following treatment with 10 Gy of 150 kVp X-rays. In vitro experiments were also performed with clonogenic assays to generate dose response curves for the same cells. Results: We observed a preferential accumulation of Au@DTDTPA:Gd in tumours; a substantial toxicity for tumour cells in vitro, but no obvious toxicity for mice; and the absence of a synergistic effect with Au@DTDTPA:Gd and radiation in all experiments. Conclusions: The additional absorption of radiation and the subsequent increase in secondary electrons, attributable to the presence of gold in Au@DTDTPA:Gd, does not lead to radiosensitisation. However, this chelating agent exhibits a chemotherapeutic action which warrants further investigation. When compared to positive results obtained by others on radiosensitisation by GNP, the present study suggests that the chemotherapeutic and radiosensitising properties of GNP may depend strongly on the nature of the coating.