Toxicity evaluation of Gd2O3@SiO2 nanoparticles prepared by laser ablation in liquid as MRI contrast agents in vivo

Abstract

Poor toxicity characterization is one obstacle to the clinical deployment of Gd 2 O 3 @ SiO 2 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.

Immuno-silent polymer capsules encapsulating nanoparticles for bioimaging applications

“…36 In another report, gadolinium nanoparticles were found to exhibit minimal immunotoxicity which was also quantified by interleukin secretions from blood serum. 37 We have demonstrated the in vitro biocompatibility and efficient internalization of PEGylated …”

Монодисперсные сферические наночастицы Gd-=SUB=-x-=/SUB=-Si-=SUB=-y-=/SUB=-O-=SUB=-z-=/SUB=- : Eu-=SUP=-3+-=/SUP=- для магнитно-резонансной томографии и оптической визуализации

“…Вследствие меньшей растворимости (произведение растворимости для Gd 2 O 3 порядка 10 −23 ) оксид гадолиния обладает меньшей токсичностью по сравнению с хелатами. Однако растворение даже незначительного количества ионов Gd 3+ из наночастиц может привести к токсическим эффектам [15].…”

Gadolinium(iii) based nanoparticles for T1-weighted magnetic resonance imaging probes

“…[39][40][41][42][43][44][45][46] The toxic effects were evaluated through the biological interaction between Gd nanoparticles with various mouse and human cells. There is a need to evaluate the potential toxicity of these Gd(III) based nanomaterial, and to investigate their bioaccumulation and clearance properties.…”

“…[39][40][41][42][43][44][45][46] The toxic effects were evaluated through the biological interaction between Gd nanoparticles with various mouse and human cells. [41][42][43][44][45][46] This review focuses on development of Gd(III)-based nanoparticles contrast agents including Gd(III) containing inorganic crystalline nanoparticles and Gd(III) chelate-graed macromolecular nanoparticles for T 1 -weighted MRI, multimodality imaging contrast agents. 39 The potential toxicity of Gd based nanoparticle depends on its constituent materials, on the chemical properties of its surface coating and on the size of the particles.…”