PT-1

Bisulfite (HSO₃^-) plays an important role in life activities. Abnormal content of HSO₃^- may cause cardiovascular, cancer and other diseases. Frequency upconverted luminescent (FUCL) probes are a class of anti-Stokes luminescent materials with long-wavelength excitation and short-wavelength emission properties, which offer advantages in a range of applications due to their higher sensitivity and photostability. In addition, FUCL imaging has the advantages of high tissue penetration depth and low photo-damage, thus, it is more suitable for fluorescence imaging. In this work, a FUCL probe based on an xanthene fluorophore was designed and synthesised to detect HSO₃^-. The Probe PT-1 could respond to HSO₃^- and had high selectivity and sensitivity. It also exhibited a quenched FUCL signal. The detection limit of FUCL concerning HSO₃^- was 43 nM (λ_ex = 730 nm), which is half the detection limit achieved under traditional excitation (93 nM, λ_ex = 643 nm). Cell fluorescence imaging showed that PT-1 could effectively target mitochondria and monitor endogenous/exogenous HSO₃^- in living cells. More importantly, PT-1 was successfully used to monitor the level of HSO₃^- in mice with drug-induced liver injury through FUCL imaging.

AMP-activated protein kinase (AMPK) is a central mediator of cellular metabolism and is activated in direct response to low ATP levels. Activated AMPK inhibits anabolic pathways and promotes catabolic activities that generate ATP through the phosphorylation of multiple target substrates. AMPK is a therapeutic target for activation in several chronic metabolic diseases, and there is increasing interest in targeting AMPK activity in cancer where it can act as a tumor suppressor or conversely it can support cancer cell survival. Small molecule AMPK activators and inhibitors have demonstrated some success in suppressing cancer growth, survival, and drug resistance in preclinical cancer models. In this perspective, we summarize the role of AMPK in cancer and drug resistance, the influence of the tumor microenvironment on AMPK activity, and AMPK activator and inhibitor development. In addition, we discuss the potential importance of isoform-selective targeting of AMPK and approaches for selective AMPK targeting in cancer.