title: Does shape matter? Bioeffects of gold nanomaterials in a human skin cell model.
abstract: Gold nanomaterials (AuNMs) have distinctive electronic and optical properties, making them ideal candidates for biological, medical, and defense applications. Therefore, it is imperative to evaluate the potential biological impact of AuNMs before employing them in any application. This study investigates two AuNMs with different aspect ratios (AR) on mediation of biological responses in the human keratinocyte cell line (HaCaT) to model potential skin exposure to these AuNMs. The cellular responses were evaluated by cell viability, reactive oxygen species (ROS) generation, alteration in gene and protein expression, and inflammatory response. Gold nanospheres, nominally 20 nm in diameter and coated with mercaptopropane sulfonate (AuNS-MPS), formed agglomerates when dispersed in cell culture media, had a large fractal dimension (D(f) = 2.57 ± 0.4) (i.e., tightly bound and densely packed) and were found to be nontoxic even at the highest dose of 100 μg/mL. Highly uniform, 16.7 nm diameter, and 43.8 nm long polyethylene glycol-capped gold nanorods (AuNR-PEG) also formed agglomerates when dispersed into the cell culture media. However, the agglomerates had a smaller fractal dimension (D(f) = 1.28 ± 0.08) (i.e., loosely bound) and were found to be cytotoxic to the HaCaT cells, with a significant decrease in cell viability occurring at 25 μg/mL and higher. Moreover, AuNR-PEG caused significant ROS production and up-regulated several genes involved in cellular stress and toxicity. These results, combined with increased levels of inflammatory and apoptotic proteins, demonstrated that the AuNR-PEG induced apoptosis. Exposure to AuNS-MPS, however, did not show any of the detrimental effects observed from the AuNR-PEG. Therefore, we conclude that shape appears to play a key role in mediating the cellular response to AuNMs.
authors.affiliation: Applied Biotechnology Branch, Human Effectiveness Directorate, 711 Human Performance Wing, Air Force Research Laboratory, Wright-Patterson AFB, Dayton, Ohio 45431, United States.
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Schaeublin
authors.forename: Laura K
authors.initials: LK
authors.lastname: Braydich-Stolle
authors.forename: Elizabeth I
authors.initials: EI
authors.lastname: Maurer
authors.forename: Kyoungweon
authors.initials: K
authors.lastname: Park
authors.forename: Robert I
authors.initials: RI
authors.lastname: MacCuspie
authors.forename: A R M Nabiul
authors.initials: AR
authors.lastname: Afrooz
authors.forename: Richard A
authors.initials: RA
authors.lastname: Vaia
authors.forename: Navid B
authors.initials: NB
authors.lastname: Saleh
authors.forename: Saber M
authors.initials: SM
authors.lastname: Hussain
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006046:Gold; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D053768:Metal Nanoparticles / Q000009:adverse effects* / Q000737:chemistry*; D049329:Nanostructures / Q000009:adverse effects* / Q000737:chemistry*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D006046:Gold