Negligible particle-specific toxicity mechanism of silver nanoparticles: The role of Ag+ ion release in the cytosol

Toxic effects of silver nanoparticles in mammals – does a risk of neurotoxicity exist?

“…This mechanism of AgNPs toxicity may be confirmed by the fact that weak antioxidants with -SH groups such as 2,3-dithiopropanol [26], N-acetylcysteine (NAC) [62], methionine and cysteine are more effective against AgNP-induced cytotoxicity than the most potent antioxidants without thiol groups such as Trolox (water soluble vitamin E analog) or Tempol [126]. Overproduction of ROS during exposure to AgNPs has been proven directly in several in vitro investigations [15,26,78,141] and also in vivo [30,103]. Among the oxidative stress-related changes caused by AgNPs, depletion of reduced glutathione (GSH) has been observed in human skin carcinoma cells [6], rat liver cells [60], mouse macrophage cells [100], human liver cells [106,141] and mouse embryonic fibroblasts [74].…”

“…For example, Ag + ions were observed to interfere with thiol groups in the mitochondrial inner membrane, increasing its permeability [5]. This mechanism of AgNPs toxicity may be confirmed by the fact that weak antioxidants with -SH groups such as 2,3-dithiopropanol [26], N-acetylcysteine (NAC) [62], methionine and cysteine are more effective against AgNP-induced cytotoxicity than the most potent antioxidants without thiol groups such as Trolox (water soluble vitamin E analog) or Tempol [126]. Overproduction of ROS during exposure to AgNPs has been proven directly in several in vitro investigations [15,26,78,141] and also in vivo [30,103].…”

“…The most effective cellular conditions for dissolving endocytosed AgNPs are found in the acidic environment of lysosomes, which has a pH of about 4.8 [26,122]. However, it has been suggested that the toxic effects are a combined result of both AgNPs and released silver ions [16,44,108,127].…”

“…Additionally, relationships between oxidative stress, autophagy and apoptosis have been demonstrated in mouse embryonic fibroblast cells [74]. Induction of apoptosis by AgNPs has been demonstrated in vitro in many types of mammalian cells, for example in THP-1 monocytes [36], human lung cancer cells [35], human liver cells [106], human colon cancer cells [118], fibroblast cells [57], mouse embryonic fibroblasts [74], HeLa cells (human cervical carcinoma), A549 cells (human lung carcinoma) [26], baby hamster kidney (BHK21) and human colon adenocarcinoma cells (HT29) [49]. It was suggested that exposure of cells to AgNPs promotes ROS-and JNK-dependent apoptotic pathways [57].…”

Effects of green-synthesized silver nanoparticles on lung cancer cells in vitro and grown as xenograft tumors in vivo

“…Researchers demonstrated the intracellular release of silver ions in HeLa and A549 cells after nanoparticle internalization, showing that in situ particle degradation is promoted by the acidic lysosomal environment and a cause-effect relationship between ions and cell death. 31 Cellular internalization of AgNPs provided the basis for the their cytotoxic activities. 38 However, more basic issues concerning the metabolism rate and internalization characteristics of AgNPs after internalization are not clearly delineated till today.…”