A Telomerase-Activated Magnetic Resonance Imaging Probe for Consecutively Monitoring Tumor Growth Kinetics and In Situ Screening Inhibitors.

Telomerase has long been considered as a biomarker for cancer diagnosis and a therapeutic target for drug discovery. Detecting telomerase activity in vivo could provide more direct information of tumor progression and response to drug treatment, which, however, is hampered by the lack of an effective probe that can generate an output signal without a tissue penetration depth limit. In this study, using the principle of distance-dependent magnetic resonance tuning, we constructed a telomerase-activated magnetic resonance imaging probe (TAMP) by connecting superparamagnetic ferroferric oxide nanoparticles (SPFONs) and paramagnetic Gd-DOTA (Gd(III) 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) complexes via telomerase-responsive DNA motifs. Upon telomerase-catalyzed extension of the primer in TAMP, Gd-DOTA-conjugated oligonucleotides can be liberated from the surface of SPFONs through a DNA strand displacement reaction, restoring the T1 signal of the Gd-DOTA for a direct readout of the telomerase activity. Here we show that, by tracking telomerase activity, this probe provides consistent monitoring of tumor growth kinetics during progression and in response to drug treatment and enables in situ screening of telomerase inhibitors in whole-animal models. This study provides an alternative toolkit for cancer diagnosis, treatment response assessment, and anticancer drug screening.

Potential obesogenic effects of TBBPA and its alternatives TBBPS and TCBPA revealed by metabolic perturbations in human hepatoma cells.

To date, increasing numbers of studies have shown the obesogenic effects of tetrabromobisphenol A (TBBPA). Tetrabromobisphenol S (TBBPS) and tetrachlorobisphenol A (TCBPA) are two common alternatives to TBBPA, and their environmental distributions are frequently reported. However, their toxicity and the associated potential health risks are poorly documented. Herein, we performed untargeted metabolomics to study the metabolic perturbations in HepG2 cells exposed to TBBPA and its alternatives. Consequently, no loss of cellular viability was observed in HepG2 cells exposed to 0.1 µmol/L and 1 µmol/L TBBPA, TBBPS and TCBPA. However, multivariate analysis and metabolic profiles revealed significant perturbations in glycerophospholipid and fatty acyl levels in HepG2 cells exposure to TBBPS and TCBPA. The evident increases in the glucose 1-phosphate and fructose 6-phosphate levels in HepG2 cells were proposed to be induced by the promotion of PGM1/PGM2 and GPI gene expression and the suppression of UPG2 and GFPT1/GFPT2 gene expression. Our results suggest that TBBPS and TCBPA are more likely to disrupt liver metabolic homeostasis and potentially drive liver dysfunction than TBBPA. Our study is significant for the re-evaluation of the health risks associated with TBBPA and its alternatives TBBPS and TCBPA.