Fig. 2: TGTA restores the anticancer activity of albumin-bound auranofin.

a a scheme for harnessing the dynamic thiol exchange to restore anticancer efficacy from albumin-bound gold. TGTA, thioglucose tetraacetate. Created in BioRender. Xiong, X. (2025) https://BioRender.com/zpgjm50. b HPLC analysis at 214 nm on the thiol exchange reaction in vitro. 1 mM of auranofin was added to 1.0 mL of 4 mM solution of BSA and then reacted at 37 °C for 60 min in a shaker. 5 mM of TGTA (5 equivalents) was used. The peak of auranofin was marked by a dotted red line. c cellular gold uptake of HCT116 cells under indicated conditions of FBS for 1 h. 3 μM of auranofin was used in all groups with or without TGTA (50 μM). The values were normalized by the protein amount extracted. Data are shown as mean ± s. d. of three independent experiments. Significance was calculated by an unpaired, two-tailed t-test. Significance was defined as p < 0.05. d dose-dependent cytotoxicity boosting of auranofin by glucose homologs after 24-hour treatments. GPA, Glucose pentaacetate. e, measuring cellular thioredoxin reductase (TrxR) activity using HCT116 upon indicated treatments. HCT116 cells in RPMI + 30% FBS were incubated with 0.5 μM auranofin and/or 50 μM TGTA for 1 h before cell lysis for TrxR activity detection. For d, e, mean ± s. d., 3 biological replicates. f mouse models to evaluate the in vivo tumor suppression of auranofin. Drugs were injected intraperitoneally 6 times per week, and the initial administration day was marked by black arrows. An HCT116 xenograft and two patient-derived xenografts (non-small cell lung carcinoma and triple-negative breast cancer) were conducted. HCT116 tumors: Vehicle, n = 7 mice; TGTA, n = 6 mice; AF, n = 6 mice; AF + TGTA, n = 9 mice. NSCLC PDX tumors: Vehicle, n = 7 mice; TGTA, n = 6 mice; AF, n = 6 mice; AF + TGTA, n = 7 mice. TNBC PDX tumors: Vehicle, n = 9 mice; TGTA, n = 9 mice; AF, n = 8 mice; AF + TGTA, n = 8 mice. Data were shown as mean ± s. e. m. Source data are provided as a Source Data file.