Multiparametric cytotoxicity assessment: the effect of gold nanoparticle ligand functionalization on SKOV3 ovarian carcinoma cell death

Abstract

Gold nanoparticles (AuNP) are promising anti-cancer agents because of their modifiable properties and high biocompatibility. This study used multiple parallel analyses to investigate the cytotoxic properties of 5 nm AuNP conjugated to four different ligands with distinct surface chemistry: polyethylene glycol (PEG), trimethylammonium bromide (TMAB), 4-dimethylaminopyridine (DMAP), and carboxyl (COOH). We used a range of biochemical and high-content microscopy methods to evaluate the metabolic function, oxidative stress, cell health, cell viability, and cell morphology in SKOV3 ovarian cancer cells. Each AuNP displayed a distinct cytotoxicity profile. All AuNP species assessed exhibited signs of dose-dependent cytotoxicity when morphology, clonogenic survival, lysosomal uptake, or cell number were measured as the marker of toxicity. All particles except for AuNP-COOH increased SKOV3 apoptosis. In contrast, AuNP-TMAB was the only particle that did not alter the metabolic function or induce significant signs of oxidative stress. These results demonstrate that AuNP surface chemistry impacts the magnitude and mechanism of SKOV3 cell death. Together, these findings reinforce the important role for multiparametric cytotoxicity characterization when considering the utility of novel particles and surface chemistries.

Keywords:

• Gold nanoparticles
• AuNP
• cytotoxicity
• nanoparticle chemistry
• cell death
• ovarian cancer
• nanotoxicology

Acknowledgements

The authors would like to thank Vett Lloyd, Tyler Lutes and Soricimed Biopharma for use of their equipment and culture facilities used to conduct these studies, Jill Downey for the purification of the AuNP-PEG’, and Stephen Cogswell for TEM imaging.

Disclosure statement

The authors report no conflict of interest.

Additional information

Funding

JLR, TJM and MVM were supported by NSERC Discovery Grants. RM was supported by Dr. L. A. Goodridge Endowment Independent Student Research Grant. MEP was supported by NSERC CGS-M.