180
Views
0
CrossRef citations to date
0
Altmetric
Research Article

Hepatotoxicity of Copper Sulfide Nanoparticles Towards Hepatocyte Spheroids Using A Novel Multi-Concave Agarose Chip Method

, , , , , , , , , , , , & show all
Pages 1487-1504 | Received 11 Jan 2021, Accepted 04 May 2021, Published online: 29 Jun 2021
 

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.

Financial & competing interests disclosure

This work was financially supported by the National Natural Science Foundation of China (nos. 31971319, 31771104), the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), and the Jiangsu Provincial Key Laboratory of Radiation Medicine and Protection. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations.

Acknowledgments

The authors would like to thank Suzhou Jestar Mold Technology Co., Ltd for the fabrication of the metal mold.

Additional information

Funding

This work was financially supported by the National Natural Science Foundation of China (nos. 31971319, 31771104), the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), and the Jiangsu Provincial Key Laboratory of Radiation Medicine and Protection. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Log in via your institution

Log in to Taylor & Francis Online

PDF download + Online access

  • 48 hours access to article PDF & online version
  • Article PDF can be downloaded
  • Article PDF can be printed
USD 99.00 Add to cart

Issue Purchase

  • 30 days online access to complete issue
  • Article PDFs can be downloaded
  • Article PDFs can be printed
USD 236.00 Add to cart

* Local tax will be added as applicable

Related Research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.