Figure 7.

(A) Schematic diagram of chemical mechanism of Ag-NP toxicity to human monocytes (THP-1). Ag-NPs are internalized by cells and trafficked from engulfed vesicles to the lysosomes. Due to the acidic environment in the lysosome, Ag-NPs in the form of (Ag0)n are dissolved into Ag+ ions and then changed into Ag-O- form possibly due to the binding of organic acid molecules. Dissolved silver increases LMPs that leads to the release of both dissolved silver and lysosomal contents to the cytoplasm. Then, both the increased LMPs and the released silver decrease the mitochondrial membrane potentials, which results in ROS generation and cell apoptosis. Meanwhile, the dissolved silver (Ag-O-) will interact with cysteine-contained proteins like metallothioneins, enzymes, etc. to become Ag-S- speciation, which may trigger mitochondrion-involved apoptosis. However, a part of Ag-S- form may be exported by the membrane transporters to reduce cytotoxicity. To understand the chemical origin of Ag-NP cytotoxicity, two advanced techniques are powerful to illustrate the dynamic processes of intracellular Ag-NPs in time and space. SR-TXM can in situ study the intracellular accumulation and exocytosis of Ag-NPs, while SRXANES is capable of revealing the chemical transformation of silver from the oxidation and degradation to the Ag-S- form. (B) TEM image of Tween-20 dispersed Ag-NPs. (C) Hydrodynamic size distributions of 10 μg mL-1 Ag-NPs during 24 h in ddH2O and 10% FBS-supplemented RPMI 1640 medium. (D and E) Cytotoxicity of Ag-NPs and Ag+ ions. (D) Impacts of Ag-NPs, Ag+ ions, and the dispersant (Tween-20) on the mitochondrial dehydrogenase activity shown as cell viability vs the dose- and time-dependence. Data are shown as mean and standard deviation (n = 4). (E) Influence of Ag-NPs, Ag+ ions and Tween-20 on the percentage of live cells determined by Live-Dead assay. Reprinted with permission from Wang L, Zhang T, Li P, et al. Use of synchrotron radiation-analytical techniques to reveal chemical origin of silver-nanoparticle cytotoxicity. ACS Nano. 2015;9(6):6532–6547. Copyright (2015) American Chemical Society.⁹⁹