Validation of an LDH Assay for Assessing Nanoparticle Toxicity

Overview

Journal Toxicology

Publisher Elsevier

Specialty Toxicology

Date 2011 Jul 5

PMID 21722700

Citations 60

Authors

Xianglu Han

Robert Gelein

Nancy Corson

Pamela Wade-Mercer

Jingkun Jiang

Pratim Biswas

Jacob N Finkelstein

Alison Elder

Gunter Oberdorster

Affiliations

Soon will be listed here.

Abstract

Studies showed that certain cytotoxicity assays were not suitable for assessing nanoparticle (NP) toxicity. We evaluated a lactate dehydrogenase (LDH) assay for assessing copper (Cu-40, 40nm), silver (Ag-35, 35nm; Ag-40, 40nm), and titanium dioxide (TiO(2)-25, 25nm) NPs by examining their potential to inactivate LDH and interference with β-nicotinamide adenine dinucleotide (NADH), a substrate for the assay. We also performed a dissolution assay for some of the NPs. We found that the copper NPs, because of their high dissolution rate, could interfere with the LDH assay by inactivating LDH. Ag-35 could also inactivate LDH probably because of the carbon matrix used to cage the particles during synthesis. TiO(2)-25 NPs were found to adsorb LDH molecules. In conclusion, NP interference with the LDH assay depends on the type of NPs and the suitability of the assay for assessing NP toxicity should be examined case by case.

Citing Articles

mRNA lipid nanoparticle formulation, characterization and evaluation.

Ma Y, VanKeulen-Miller R, Fenton O Nat Protoc. 2025; .

PMID: 40069324 DOI: 10.1038/s41596-024-01134-4.

Save Your Tears for the Toxicity Assays-Carbon Nanotubes Still Fooling Scientists.

Suni J, Valkama S, Peltola E ACS Omega. 2025; 10(6):5554-5562.

PMID: 39989827 PMC: 11840583. DOI: 10.1021/acsomega.4c08211.

Copper-enriched hydroxyapatite coatings obtained by high-velocity suspension flame spraying. Effect of various gas parameters on biocompatibility.

Le L, Lanzino M, Blum M, Hoppel A, Al-Ahmad A, Killinger A J Mater Sci Mater Med. 2024; 35(1):70.

PMID: 39614935 PMC: 11608161. DOI: 10.1007/s10856-024-06846-3.

Differentially Induced Autophagy by Engineered Nanomaterial Treatment Has an Impact on Cellular Homeostasis and Cytotoxicity.

Alcolea-Rodriguez V, Dumit V, Ledwith R, Portela R, Banares M, Haase A Nano Lett. 2024; 24(38):11793-11799.

PMID: 39271139 PMC: 11440646. DOI: 10.1021/acs.nanolett.4c01573.

Harvesting methods of umbilical cord-derived mesenchymal stem cells from culture modulate cell properties and functions.

Nakao M, Nagase K Regen Ther. 2024; 26:80-88.

PMID: 38841206 PMC: 11152751. DOI: 10.1016/j.reth.2024.05.010.

References

Rushton E, Jiang J, Leonard S, Eberly S, Castranova V, Biswas P . Concept of assessing nanoparticle hazards considering nanoparticle dosemetric and chemical/biological response metrics. J Toxicol Environ Health A. 2010; 73(5):445-61. PMC: 3884809. DOI: 10.1080/15287390903489422. View

Chen Z, Meng H, Xing G, Chen C, Zhao Y, Jia G . Acute toxicological effects of copper nanoparticles in vivo. Toxicol Lett. 2005; 163(2):109-20. DOI: 10.1016/j.toxlet.2005.10.003. View

Hikosaka K, Kim J, Kajita M, Kanayama A, Miyamoto Y . Platinum nanoparticles have an activity similar to mitochondrial NADH:ubiquinone oxidoreductase. Colloids Surf B Biointerfaces. 2008; 66(2):195-200. DOI: 10.1016/j.colsurfb.2008.06.008. View

Maxim L, Hadley J, Potter R, Niebo R . The role of fiber durability/biopersistence of silica-based synthetic vitreous fibers and their influence on toxicology. Regul Toxicol Pharmacol. 2006; 46(1):42-62. DOI: 10.1016/j.yrtph.2006.05.003. View

Karajanagi S, Vertegel A, Kane R, Dordick J . Structure and function of enzymes adsorbed onto single-walled carbon nanotubes. Langmuir. 2004; 20(26):11594-9. DOI: 10.1021/la047994h. View

Koslowski R, Barth K, Augstein A, Tschernig T, Bargsten G, Aufderheide M . A new rat type I-like alveolar epithelial cell line R3/1: bleomycin effects on caveolin expression. Histochem Cell Biol. 2004; 121(6):509-19. DOI: 10.1007/s00418-004-0662-4. View

Worle-Knirsch J, Pulskamp K, Krug H . Oops they did it again! Carbon nanotubes hoax scientists in viability assays. Nano Lett. 2006; 6(6):1261-8. DOI: 10.1021/nl060177c. View

Grof P, Aslanian D, RONTO G . Changes of phage T7 nucleoprotein structure at low ionic strength. A Raman spectroscopic study. Biochim Biophys Acta. 1996; 1289(1):95-104. DOI: 10.1016/0304-4165(95)00151-4. View

Huang X, El-Sayed I, Yi X, El-Sayed M . Gold nanoparticles: catalyst for the oxidation of NADH to NAD(+). J Photochem Photobiol B. 2005; 81(2):76-83. DOI: 10.1016/j.jphotobiol.2005.05.010. View

10.

Linse S, Cabaleiro-Lago C, Xue W, Lynch I, Lindman S, Thulin E . Nucleation of protein fibrillation by nanoparticles. Proc Natl Acad Sci U S A. 2007; 104(21):8691-6. PMC: 1866183. DOI: 10.1073/pnas.0701250104. View

11.

Cedervall T, Lynch I, Foy M, Berggard T, Donnelly S, Cagney G . Detailed identification of plasma proteins adsorbed on copolymer nanoparticles. Angew Chem Int Ed Engl. 2007; 46(30):5754-6. DOI: 10.1002/anie.200700465. View

12.

Breccia J, Andersson M, Hatti-Kaul R . The role of poly(ethyleneimine) in stabilization against metal-catalyzed oxidation of proteins: a case study with lactate dehydrogenase. Biochim Biophys Acta. 2002; 1570(3):165-73. DOI: 10.1016/s0304-4165(02)00193-9. View

13.

Jenkins R, Tanner M . Ionic-strength-dependent changes in the structure of the major protein of the human erythrocyte membrane. Biochem J. 1977; 161(1):131-8. PMC: 1164481. DOI: 10.1042/bj1610131. View

14.

Chen C, Yamaguchi T, Sugawara K, Koga K . Role of stress in the self-limiting oxidation of copper nanoparticles. J Phys Chem B. 2006; 109(44):20669-72. DOI: 10.1021/jp0546498. View

15.

Eastes W, Hadley J . Role of fiber dissolution in biological activity in rats. Regul Toxicol Pharmacol. 1994; 20(3 Pt 2):S104-12. View