Figure 8

Cationic Au-NPs trigger apoptosis. (A) THP-1 cells were exposed for 24 h to Au-5-NR3+ NPs, or Au-20-NR3+ NPs (25 µg/mL). STS (4 µM) was used as positive control for apoptotic cell death. To determine the role of autophagy, cells were pre-incubated for 1 h with 3-MA (1 mM) (B) or wortmannin (1 µM) (C) prior to the exposure to NPs. Alternatively, cells were pre-incubated with the pan-caspase inhibitor, zVAD-fmk (20 µM) (D) to block caspase activity. Cells were then fixed and incubated with propidium iodide/RNAse A, and DNA content was analyzed by flow cytometry. Data are mean values of 3 experiments ± S.D. *P ≤ 0.05, ** ≤ 0.01, and *** ≤ 0.001 (treatment versus control). For corresponding results on caspase activation, refer to Supplementary Fig. S4. (E) Schematic diagram summarizing the impact of cationic Au-NPs on cells leading to mitochondrial dysfunction and apoptosis and a cytoprotective, autophagic response. At higher concentrations of Au-NPs and/or following prolonged exposure, cellular ATP levels are dissipated and the cells succumb to necrotic cell death (refer to Supplementary Fig. S5).