Inhibition of enzyme activity by nanomaterials: Potential mechanisms and implications for nanotoxicity testing

Abstract

The objective of this study was to investigate whether nanoparticle-exposure affects enzyme function and to determine the mechanisms responsible. Silicon, Au, and CdSe nanoparticles were synthesized in house and their physicochemical properties were characterized. The activity of purified lactate dehydrogenase (LDH) was inhibited or abolished by all nanoparticles tested. Inhibition was dependent upon particle core and surface-functional group composition. Inhibition of LDH was absent in crude tissue homogenates, in the presence of albumin, and at the isoelectric point of the protein, indicating that nanoparticles bind non-specifically to abundant proteins via a charge interaction. Circular dichroism spectroscopy suggests that the structure of LDH may be altered by nanoparticles in a manner different from that of bulk controls. We present new data on the specific physicochemical properties of nanoparticles that may lead to bioactivity and highlight a number of potentially serious problems with common nanotoxicity testing methods.

Keywords::

• Nanotoxicology
• nanoparticles
• ecotoxicology
• biochemistry
• toxicology

Acknowledgements

The authors would like to thank Dr Tony Yeung for the use of ζ potential and particle sizing equipment and Craig Turk and David Zinz for the collection circular dichroism data. The authors also thank Dr Jason Treberg for methodological assistance and Dr Sean Dalrymple for help with the interpretation of literature crystal structure data.

Declaration of interest: Research was funded by an Izaak Walton Killam Foundation PDF (TJM), the Natural Sciences and Engineering Research Council of Canada Strategic Grants program (JGCV and GGG), an Alberta Ingenuity Centre for Water Research grant (GGG), and an NSERC-NRC-BDC-EC grant (GGG and JGV). The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.