. Author manuscript; available in PMC: 2016 May 7.

Published in final edited form as: Nanoscale. 2015 May 7;7(17):7470–7481. doi: 10.1039/c5nr01133g

Table 2.

Detrimental effects induced by nAg on different cells.

Characteristics of nAg	Cell types	Doses (cell viability)	ROS levels	Major conclusions	Ref.
6–20 nm, starch coating	Human lung fibroblast IMR-90 and human glioblastoma cell line U251	25–400 µg mL⁻¹	Increased	Intracellular nAg, uptake mainly through macropinocytosis and clathrin-dependent endocytosis, induced stress responses, chromosomal abnormalities and proliferation inhibition	⁷⁵
43.9 nm, sphere, citrate coating	Murine macrophage line RAW 264.7	30–100 µg mL⁻¹ (from less than 40% to 90%)	Increased	Uptake and localization of nAg in cells resulted in oxidative stress and cell apoptosis	⁷⁴
15, 100 nm, no coating	Rat liver cell line BRL 3A	5–50 µg mL⁻¹ (from less than 20% to 70%)	Increased	Increased LDH leakage and dysfunction of mitochondria, along with ROS generation, contributed to cellular morphological modifications	³²
15, 30 and 55 nm, no coating	Rat alveolar macrophages	10–75 µg mL⁻¹ (from less than 20% to 80%)	Increased	Oxidative stress induced mitochondrial function reduction, membrane leakage increase and inflammatory response in a size-dependent manner	³¹
1–100 nm, no coating	Mouse fibroblast NIH 3T3	50–100 µg mL⁻¹ (less than 50%)	Increased	ROS generation and JNK activation triggered mitochondrial-dependent apoptosis	⁹¹
≤ 100 nm, no coating	Human Chang liver cells and Chinese hamster lung fibroblasts	3–4 µg mL⁻¹ (50%)	Not reported	Endoplasmic reticulum stress signaling mediated cellular apoptosis	⁹²
26.2 ± 7.6 nm, sphere, citrate coating	Mouse fibroblast NIH 3T3	2–30 µg mL⁻¹ (from less than 50% to 95%)	Increased	ROS generation resulted in cellular morphological abnormalities, autophagy dysfunction and cell death	⁹⁰
5, 28 and 100 nm, sphere, PVP coating	Human blood monocytes	0.3–1.25 µg mL⁻¹ (from less than 40% to 80%)	Increased	Enhanced hydrogen peroxide caused mitochondrial membrane superoxide, resulting in inflammasome formation and cytokine IL-1β release	⁸⁷
65 nm, sphere, citrate coating	Human umbilical vein endothelial cells	1–2 µg mL⁻¹ (from less than 10% to 90%)	Increased	Oxidative damage led to in cell dysfunction and apoptosis following NF κB activation	⁸⁸
25 nm, polysaccharide coating versus no coating	Mouse embryonic stem cells and mouse embryonic fibroblasts	50 µg mL⁻¹ (less than 60%)	Not reported	Coated nAg elicited more severe DNA damage and apotosis than uncoated	⁸⁹
6–20 nm, sphere, starch coating	Human lung fibroblast cell line IMR-90 and human glioblastoma cell line U251	25–400 µg mL⁻¹ (from less than 20% to 90%)	Increased	Disruption of the mitochondrial respiratory chain resulted in ROS production and ATP synthesis reduction, leading to DNA damage and cell cycle arrest	⁷⁰
5–10 nm, no coating	Human Jurkat T cells	0.05–0.2 µg mL⁻¹ (70–90%)	Increased	Oxidative damage led to DNA strand breaks, cell cycle arrest and apoptosis	⁹⁶
15.9 ± 7.6 nm, sphere, citrate coating	Human lung epithelial cell line A549	12.1 µg/ml (80%)	Increased	Up-regulated expression of stress response-related genes caused cell cycle arrest	¹⁰³
10, 20, and 40 nm, sphere, PVP coating; 45 × 10 nm, plate, PVP coating; 60 nm × 20 µm, wires, PVP coating	Rainbow trout gill fish cell line RT-W1	0.39–25 µg mL⁻¹	Increased	High surface reactivity are responsible for contributing to shape-dependent effects of cell membrane lysis	⁵³
57.7 ± 6.9 nm, sphere, PEG coating	Murine macrophage cell line J774A.1	1.2–8.7 µg mL⁻¹ (100%)	Not reported	Scavenger receptor-mediated phagocytosis and clathrin- and actin-dependent endocytosis coexisted in cellular uptake of nAg	⁷³
10, 40 and 75 nm, citrate coating; 10 nm, PVP coating; 50 nm, no coating	Bronchial epithelial cell line BEAS-2B	5–50 µg mL⁻¹ (from less than 20% to 100%)	Not detected	Cellular uptake, intracellular localization and Ag release were responsible for size-dependent cytotoxicity	⁵⁶
10, 25 and 40 nm, sphere, PVP coating; 45 × 10 nm, plate, PVP coating	Human embryonic kidney cell line EK293T, human cervical cancer cell line HeLa, human prostate cancer cell line PC3, human hepatic carcinoma cell line HepG2, and human renal carcinoma cell line A498	2–8 µg mL⁻¹ (100%)	Not detected	Changes of energy metabolism-related gene expression and protein levels resulted in cellular energy reprogramming in a size- and shape-dependent manner	³⁵
7–10 nm, no coating	Human hepatic carcinoma cell line HepG2	0.1–3 µg mL⁻¹ (from less than 50% to 160%)	Not detected	A number of genes related to cell proliferation and cell cycle, not stress response, were up-regulated under a nontoxic dose	³⁴
10, 25, 40 and 110 nm, sphere, PVP coating; 45 × 10 nm, plate, PVP coating	Mouse erythroleukemia cells	1–8 µg mL⁻¹ (100%)	Not detected	Reciprocal interaction between nAg with RNA polymerase resulted in a robust inhibition on overall RNA transcription	³⁶

ROS, reactive oxygen species; PVP, polyvinylpyrrolidone; PEG, polyethylene glycols; LDH, lactate dehydrogenase; JNK, c-Jun N-terminal kinases