Hypoxia imaging in cells and tumor tissues using a highly selective fluorescent nitroreductase probe.

Hypoxia is a characteristic of locally advanced solid tumors, resulting from an imbalance between oxygen consumption and supply. In hypoxic solid tumors, an increased expression of nitroreductase (NTR) is detected, therefore, the development of NTR-targeted fluorescent probes to selectively and efficiently detect hypoxia in vivo is of utmost importance. In this study, a probe (1) has been designed and tested for effective optical detection of NTR in vitro and in vivo. The reduction of probe (1), catalyzed by NTR, resulted in changes of the electron-withdrawn nitrogen group into an electron-donation amino group. In addition, breakage of the O-C bond ensured selective fluorescence enhancement. The in vitro response towards exogenous NTR, from rat liver microsomes, resulted in the optical enhancement during the detection process. In vivo imaging of caerorhabditis elegans (C.elegan) further confirmed the detection of NTR by probe (1). Moreover, probe (1) was successfully used for the detection of hypoxia in both HI5 cells, and a murine tumor model, which demonstrates the potential of probe (1) for application in fluorescence bioimaging studies, and tumor hypoxia diagnosis.

Highly selective in vivo imaging of endogenous/exogenous phosphate ion over ATP and PPi.

A chemodosimeter was designed to function as a highly selective phosphate ion (Pi ) sensor, showing a 91-fold ratiometric fluorescence enhancement. The probe successfully visualized exogenous and endogenous apyrase-catalyzed Pi generation and was the first probe able to trace the generation and enrichment of Pi through hemichannel closure in Sf9 cells.