Gold nanoparticles cellular toxicity and recovery: Effect of size, concentration and exposure time

Abstract

Gold nanoparticles (AuNPs) are used in many applications; however, their interactions with cells and potential health risk(s) are not fully known. In this manuscript, we describe the interactions of AuNPs with human dermal fibroblasts and show that they can penetrate the plasma membrane and accumulate in large vacuoles. We also demonstrate that the uptake of the AuNPs is a function of time, their size and concentration. Specifically, we demonstrate that 45 nm AuNPs penetrate cells via clathrin-mediated endocytosis, while the smaller 13 nm enter mostly via phagocytosis. Furthermore, we provide evidence of cytoskeleton filament disruption as a result of AuNPs exposure and reconstitution during recovery (following AuNP removal), despite no changes in actin or beta-tubulin protein levels. In contrast, the expression of the extracellular matrix (ECM) proteins, collagen and fibronectin, was diminished in the cells exposed to AuNPs. We also examined the proliferation rates of cells exposed to AuNPs and show that its diminution is a function of apoptosis and speculate that apoptosis results from the number of vacuoles present in the cells, which is probably the main factor that disrupts the cytoskeleton causing cell area contraction and decreases in motility. Lastly, we also present data that indicates that AuNPs' damage to cells is not permanent and that the cells can completely recover as a function of AuNPs' size, concentration and exposure time. Taken together, our data suggest that AuNPs exert detrimental effects on cell function that could reverse following AuNPs removal.

Effects of humic acid and ionic strength on TiO2 nanoparticles sublethal toxicity to zebrafish

“…Nanomaterials with smaller size are theoretically expected to be more toxic than their bigger counterparts due to the greater surface reactivity and ability to penetrate into and accumulate within cells and organisms (Ispas et al Mironava et al 2010). Unsuccessfully, no discernable correlation between primary particle size and toxic effect were found, thus it was assumed that secondary particle size and particle surface area may be refer to biological potential of nanoparticles although insufficient confirmatory data exist (Menard et al 2011).…”

Effects of nano-scale TiO2, ZnO and their bulk counterparts on zebrafish: Acute toxicity, oxidative stress and oxidative damage

“…Nanomaterials are theoretically expected to be more toxic than their bulk counterparts due to their greater surface reactivity and the ability to penetrate into and accumulate within cells and organisms (Carlson et al, 2008;Ispas et al, 2009;Mironava et al, 2010). However, investigations of aggregations of NPs with size distributions similar to those of their bulk particles in suspension have revealed that the toxicity mechanisms of NPs are more complex (Warheit et al, 2006;Zhang et al, 2008).…”

Gold nanoparticles explore cells: Cellular uptake and their use as intracellular probes

“…charge, surface modification, particle size and shape [35][36][37][38][39] as well as experimental procedures involving concentration and exposure time [40]. Different cellular mechanisms are involved in particle uptake such as phagocytosis and pinocytosis.…”

“…The latter facilitates the uptake process through small membrane-bound vesicles, called endosomes. [41,42] Pinocytosis can involve energy-dependent and receptor mediated endocytosis which has been shown to be the dominant internalisation pathway for several cell lines [36,40,43]. Following internalisation, membrane-bound vesicles encapsulating the particles mature and eventually fuse with lysosomes [41].…”