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Updated: Oct 31, 2025
Advanced 3D Liver Models for In vitro Genotoxicity Testing Following Long-Term Nanomaterial Exposure
Published on: June 5, 2020
Hepatotoxicity of copper sulfide nanoparticles towards hepatocyte spheroids using a novel multi-concave agarose chip
Tianyan Jiang1, Haoxiang Guo1, Ya-Nan Xia1
1School of Radiation Medicine & Protection, State Key Laboratory of Radiation Medicine & Protection, School for Radiological & Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou, 215123, PR China.
Abstract:
Aim: To explore the hepatotoxicity of copper sulfide nanoparticles (CuSNPs) toward hepatocyte spheroids. Materials & methods: Other than the traditional agarose method to generate hepatocyte spheroids, we developed a multi-concave agarose chip (MCAC) method to investigate changes in hepatocyte viability, morphology, mitochondrial membrane potential, reactive oxygen species and hepatobiliary transporter by CuSNPs. Results: The MCAC method allowed a large number of spheroids to be obtained per sample. CuSNPs showed hepatotoxicity in vitro through a decrease in spheroid viability, albumin/urea production and glycogen deposition. CuSNPs also introduced hepatocyte spheroid injury through alteration of mitochondrial membrane potential and reactive oxygen species, that could be reversed by N-acetyl-l-cysteine. CuSNPs significantly decreased the activity of BSEP transporter by downregulating its mRNA and protein levels. Activity of the MRP2 transporter remained unchanged. Conclusion: We observed the hepatotoxicity of CuSNPs in vitro with associated mechanisms in an advanced 3D culture system.
