Uptake of gold nanoparticles in murine macrophage cells without cytotoxicity or production of pro-inflammatory mediators

Abstract

More information characterizing the biological responses to nanoparticles is needed to allow the U.S. Food and Drug Administration to evaluate the safety and effectiveness of products with nano-scale components. The potential cytotoxicity and inflammatory responses of Au NPs (60 nm, NIST standard reference materials) were investigated in murine macrophages. Cytotoxicity was evaluated by MTT and LDH assays. Cytokines (IL-6, TNF-α), nitric oxide, and ROS were assayed to assess inflammatory responses. Morphological appearance and localization of particles were examined by high resolution illumination microscopy, transmission electron microscopy (TEM), and scanning TEM coupled with EDX spectroscopy. Results showed no cytotoxicity and no elevated production of proinflammatory mediators; however, imaging analyses demonstrated cellular uptake of Au NPs and localization within intracellular vacuoles. These results suggest that 60 nm Au NPs, under the exposure conditions tested, are not cytotoxic, nor elicit pro-inflammatory responses. The localization of Au NPs in intracellular vacuoles suggests endosomal containment and an uptake mechanism involving endocytosis.

Keywords::

• Gold nanoparticles
• macrophages
• cytotoxicity
• inflammation
• cytokine

Acknowledgements

This work was supported by U.S. Food and Drug Administration nanotechnology research funds. We would also acknowledge the Research Fellowship Program support administered by the Oak Ridge Research Fellowship Program (ORISE) Associated University through a contract with the U.S. Food and Drug Administration.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper. The conclusions and opinions in this report are those of the authors and do not constitute FDA policy, and the mention of any products and/or manufacturers does not imply FDA endorsement.