Cellular recognition and trafficking of amorphous silica nanoparticles by macrophage scavenger receptor A

Abstract

The cellular uptake of engineered nanoparticles (ENPs) is known to involve active transport mechanisms, yet the biological molecules involved are poorly understood. We demonstrate that the uptake of amorphous silica ENPs by macrophage cells, and the secretion of proinflammatory cytokines, is strongly inhibited by silencing expression of scavenger receptor A (SR-A). Conversely, ENP uptake is augmented by introducing SR-A expression into human cells that are normally non-phagocytic. Confocal microscopy analyses show that the majority of single or small clusters of silica ENPs co-localize with SR-A and are internalized through a pathway characteristic of clathrin-dependent endocytosis. In contrast, larger silica ENP agglomerates (>500 nm) are poorly co-localized with the receptor, suggesting that the physical agglomeration state of an ENP influences its cellular trafficking. As SR-A is expressed in macrophages throughout the reticulo-endothelial system, this pathway is likely an important determinant of the biological response to ENPs.

Keywords::

• Scavenger receptor
• silica
• nanoparticle
• endocytosis
• macrophage

Acknowledgments

The authors thank Dr Joel Pounds for critical review and discussions, and Mr Matt Littke for experimental support. Support for this work was provided by the National Institutes of Health (ES016212, BDT), the Environmental Protection Agency (STAR grant RD833338, GO), Air Force Research Laboratory (FA8650-05-1-504 to ONAMI-SNNI), and the Multi-scale Toxicology Research Initiative sponsored by Battelle Memorial Institute (CRADA #PNNL/284). Portions of this work were conducted at the Environmental Molecular Science Laboratory at Pacific Northwest National Laboratory, a U.S. Department of Energy national user facility. PNNL is operated by Battelle for the U.S. Department of Energy under contract AC06-76RLO 1830.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.