A New Strategy toward “Simple” Water‐Soluble AIE Probes for Hypoxia Detection

Abstract Hypoxia‐responsive fluorescent probes have emerged as a novel scaffold for tumor diagnosis. However, dilemma often exists between simple synthesis and high water solubility in traditional probes. Owing to the intrinsic property of N‐oxides, herein, a new strategy is proposed to design and synthesize probes for in vitro hypoxia imaging. Equipped with tetraphenylethene (TPE), the N‐oxides exhibit aggregation‐induced emission characteristics and emit no light in aqueous solutions. Interestingly, the N‐oxides can be reduced by ferrous ions in different rates. The aggregation of the resulting hydrophobic TPE residues restricts the intramolecular motions of the molecules, which “turns‐on” their fluorescence. The NO covalent bond of one molecule can be specifically cleaved by cellular reductase overexpressed under hypoxic conditions, and thus turn‐on hypoxia imaging in vitro is achieved. The new strategy to design hypoxia imaging probes is extremely valuable and has great potential for application in tumor diagnosis.