title: 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.
authors.affiliation: Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada. tmaccormack@mta.ca
authors.forename: Tyson J
authors.initials: TJ
authors.lastname: Maccormack
authors.forename: Rhett J
authors.initials: RJ
authors.lastname: Clark
authors.forename: Michael K M
authors.initials: MK
authors.lastname: Dang
authors.forename: Guibin
authors.initials: G
authors.lastname: Ma
authors.forename: Joel A
authors.initials: JA
authors.lastname: Kelly
authors.forename: Jonathan G C
authors.initials: JG
authors.lastname: Veinot
authors.forename: Greg G
authors.initials: GG
authors.lastname: Goss
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002942:Circular Dichroism; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D053768:Metal Nanoparticles / Q000633:toxicity*; D011817:Rabbits; D018675:Toxicity Tests
chemical_list: D007770:L-Lactate Dehydrogenase