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Toxicity evaluation of [email protected] nanoparticles prepared by laser ablation in liquid as MRI contrast agents in vivo.

Tian X1, Yang F1, Yang C2, Peng Y1, Chen D3, Zhu J1, He F1, Li L2, Chen X1.

Int J Nanomedicine. 2014 Aug 21;9:4043-53.

 

1Department of Biomedical Engineering, Guangzhou Medical University, Guangzhou, Guangdong Province, People’s Republic of China.and

2State Key Laboratory of Oncology in South China, Imaging Diagnosis and Interventional Center, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong Province, People’s Republic of China.and

3State Key Laboratory of Optoelectronic Materials and Technologies, School of Physics and Engineering, Sun Yat-Sen University, Guangzhou, Guangdong Province, People’s Republic of China.

 

Abstract

Poor toxicity characterization is one obstacle to the clinical deployment of [email protected] SiO2 core-shell nanoparticles (Gd-NPs) for use as magnetic resonance (MR) imaging contrast agents. To date, there is no systematic toxicity data available for Gd-NPs prepared by laser ablation in liquid. In this article, we systematically studied the Gd-NPs’ cytotoxicity, apoptosis in vitro, immunotoxicity, blood circulation half-life, biodistribution and excretion in vivo, as well as pharmacodynamics. The results show the toxicity, and in vivo MR data show that these NPs are a good contrast agent for preclinical applications. No significant differences were found in cell viability, apoptosis, and immunotoxicity between our Gd-NPs and Gd in a DTPA (diethylenetriaminepentaacetic acid) chelator. Biodistribution data reveal a greater accumulation of the Gd-NPs in the liver, spleen, lung, and tumor than in the kidney, heart, and brain. Approximately 50% of the Gd is excreted via the hepatobiliary system within 4 weeks. Furthermore, dynamic contrast-enhanced T1-weighted MR images of xenografted murine tumors were obtained after intravenous administration of the Gd-NPs. Collectively, the single step preparation of Gd-NPs by laser ablation in liquid produces particles with satisfactory cytotoxicity, minimal immunotoxicity, and efficient MR contrast. This may lead to their utility as molecular imaging contrast agents in MR imaging for cancer diagnosis.

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