Dynamic protein coronas revealed as a modulator of silver nanoparticle sulphidation in vitro

Abstract

Proteins adsorbing at nanoparticles have been proposed as critical toxicity mediators and are included in ongoing efforts to develop predictive tools for safety assessment. Strongly attached proteins can be isolated, identified and correlated to changes in nanoparticle state, cellular association or toxicity. Weakly attached, rapidly exchanging proteins are also present at nanoparticles, but are difficult to isolate and have hardly been examined. Here we study rapidly exchanging proteins and show for the first time that they have a strong modulatory effect on the biotransformation of silver nanoparticles. Released silver ions, known for their role in particle toxicity, are found to be trapped as silver sulphide nanocrystals within the protein corona at silver nanoparticles in serum-containing cell culture media. The strongly attached corona acts as a site for sulphidation, while the weakly attached proteins reduce nanocrystal formation in a serum-concentration-dependent manner. Sulphidation results in decreased toxicity of Ag NPs.

Inactivation, Clearance, and Functional Effects of Lung-Instilled Short and Long Silver Nanowires in Rats

“…There was a relatively mild transient degree of inflammatory response with little evidence of an oxidative stress or protein exudation, but associated with an acute release of cytokines. The mild inflammatory response may be linked to the dissolution and transformation of the surface of the AgNWs to Ag 2 S seen intracellularly, here in ATII cells, and also inside J774 macrophage cells in vitro , 16 and hence their inactivation leads to a reduced dissolution rate of the nanowires.…”

“…18 This process of NP sulfidation has also been observed when AgNPs were incubated with a J774 macrophage cell line in vitro. (16) We suggested that sulfidation occurred through the action of sulfide species, including H 2 S, HS – , or S 2– , which are present inside human lung tissues. Since no evidence of cytotoxicity was observed, we proposed that the precipitation of Ag + ions released from the AgNWs as highly insoluble Ag 2 S may act as a detoxification mechanism that could limit their short-term toxicological effects.…”

“…This process of intracellular transformation has been demonstrated in our previous work for a single AgNW length in in vitro cell cultures, 15 and a recent study demonstrated the intracellular transformation of spherical AgNPs into nano-Ag 2 S on the surface. 16 There is no evidence so far that this process occurs in vivo . There is also no understanding of how this high aspect ratio nanomaterial is distributed, internalized, and transformed inside lung cells in vivo , how this process is influenced by AgNW length, and whether these processes could be correlated to inflammatory responses, pulmonary function and responsiveness, and the persistence of silver in the lungs.…”

Biosilver nanoparticle interface offers improved cell viability

“…Coating or functionalising silver NPs’ surfaces with polymers or biomolecules, including proteins, alters the silver NPs’ size and properties due to the formation of a coronal structure formed upon subsequent contact with biological fluids from host tissues. 3,30,33,36,51 Hard and soft coronal structures and compositions alter the silver NP structure and size and therefore can affect both their innate antimicrobial properties and cellular cytotoxicity. 33,35 The effects of the transient, soft corona layer on silver NP function and cellular uptake have not yet been studied in detail due to the inability to distinguish accurately the rapidly exchanging, weakly bound proteins in various biological environments.…”

“…33,35 The effects of the transient, soft corona layer on silver NP function and cellular uptake have not yet been studied in detail due to the inability to distinguish accurately the rapidly exchanging, weakly bound proteins in various biological environments. 51 However, the sustained complex protein corona properties have been linked to NP aggregation and cellular association. 36,51 Agglomeration substantially reduces the antimicrobial capacity of silver NPs, so maintaining a dispersed and stable silver NP population is critical.…”