Fig. 3

Cytotoxicity and cellular energetic assays. SAD SiNPs demonstrated rapid cytotoxic effects on HK-2 cells (A) which were preceded by significant reductions to mitochondrial activity (B) and hyperpolarization of mitochondrial membranes (C). Although pristine 200 nm SiNPs had minimal effects on viability and mitochondrial activity, treatment did result in some degree of mitochondrial membrane depolarization. SAD SiNPs were found to inhibit mitochondrial respiration (D) as soon as 3 min post injection. Cells treated with higher concentrations (25 µg/mL) demonstrated a loss of oligomycin response (E) while still retaining some degree of response to FCCP, potentially indicating a loss of ATP production dependent on mitochondrial membrane permeability. All treatments resulted in increased glycolytic activity (F), while SAD SiNP exposure also resulted in a loss of glycolytic reserve (G) as indicated by a reduced/reversed response to oligomycin. Data is presented as mean and SEM with values normalized to vehicle treated control cells in figures A-C and normalized to cells prior to treatment in figures D-G (N = 3). Data was analyzed with one-way ANOVA (P value: <0.0001) and Dunnett’s multiple comparison test for group-to-control comparisons (**** indicates a P value: <0.0001). In time course experiments, **** indicates the earliest timepoint that experienced significant differences