A mitochondria-targeted chemiluminescent probe for detection of hydrogen sulfide in cancer cells, human serum and in vivo.

Hydrogen sulfide (H2S) as a critical messenger molecule plays vital roles in regular cell function. However, abnormal levels of H2S, especially mitochondrial H2S, are directly correlated with the formation of pathological states including neurodegenerative diseases, cardiovascular disorders, and cancer. Thus, monitoring fluxes of mitochondrial H2S concentrations both in vitro and in vivo with high selectivity and sensitivity is crucial. In this direction, herein we developed the first ever example of a mitochondria-targeted and H2S-responsive new generation 1,2-dioxetane-based chemiluminescent probe (MCH). Chemiluminescent probes offer unique advantages compared to conventional fluorophores as they do not require external light irradiation to emit light. MCH exhibited a dramatic turn-on response in its luminescence signal upon reacting with H2S with high selectivity. It was used to detect H2S activity in different biological systems ranging from cancerous cells to human serum and tumor-bearing mice. We anticipate that MCH will pave the way for development of new organelle-targeted chemiluminescence agents towards imaging of different analytes in various biological models.

A hydrogen sulfide and tyrosinase responsive dual-locked fluorophore for selective imaging of melanoma cells.

A resorufin-based dual-locked fluorescent probe (RHT) was introduced to image melanoma cells selectively. RHT was shown to function as an AND molecular logic gate as it emitted a signal only in the presence of both hydrogen sulfide (H2S) and tyrosinase (Tyr), which are known to be overexpressed in melanoma cells. In vitro cell culture studies revealed that RHT can be activated with endogenous H2S and Tyr and allows selective imaging of B16-F10 cancer cells under confocal microscopy. RHT marks the first ever example of a fluorescent probe that is sequentially activated by H2S and Tyr.

Real-time visualization of butyrylcholinesterase activity using a highly selective and sensitive chemiluminescent probe.

Butyrylcholinesterase (BChE), one of the critical human cholinesterases, plays crucial roles in numerous physiological and pathological processes. Accordingly, it is a striking and at the same time challenging target for bioimaging studies. Herein, we developed the first ever example of a 1,2-dixoetane-based chemiluminescent probe (BCC) for monitoring BChE activity in native biological contexts such as living cells and animals. BCC was initially shown to exhibit a highly selective and sensitive turn-on response in its luminescence signal upon reacting with BChE in aqueous solutions. Later, BCC was utilized to image endogenous BChE activity in normal and cancer cell lines. It was also shown through inhibition experiments that BChE can detect fluctuations of BChE levels successfully. In vivo imaging ability of BCC was demonstrated in healthy and tumor-bearing mice models. BCC enabled us to visualize the BChE activity in different regions of the body. Furthermore, it was successfully employed to monitor tumors derived from neuroblastoma cells with a very high signal to noise ratio. Thus, BCC appears as a highly promising chemiluminescent probe, which can be used to further understand the contribution of BChE to regular cellular processes and the formation of diseased states.

Glutamate Scavenging as a Neuroreparative Strategy in Ischemic Stroke.

Stroke is the second highest reason of death in the world and the leading cause of disability. The ischemic stroke makes up the majority of stroke cases that occur due to the blockage of blood vessels. Therapeutic applications for ischemic stroke include thrombolytic treatments that are in limited usage and only applicable to less than 10% of the total stroke patients, but there are promising new approaches. The main cause of ischemic neuronal death is glutamate excitotoxicity. There have been multiple studies focusing on neuroprotection via reduction of glutamate both in ischemic stroke and other neurodegenerative diseases that ultimately failed due to the obstacles in delivery. At that point, systemic glutamate grabbing, or scavenging is an ingenious way of decreasing glutamate levels upon ischemic stroke. The main advantage of this new therapeutic method is the scavengers working in the circulating blood so that there is no interference with the natural brain neurophysiology. In this review, we explain the molecular mechanisms of ischemic stroke, provide brief information about existing drugs and approaches, and present novel systemic glutamate scavenging methods. This review hopefully will elucidate the potential usage of the introduced therapeutic approaches in stroke patients.