Affiliation:
1. School of Chemistry and Molecular Engineering Shanghai Key Laboratory of Functional Materials Chemistry Key Laboratory for Advanced Materials and Institute of Fine Chemicals Joint International Research Laboratory of Precision Chemistry and Molecular Engineering Feringa Nobel Prize Scientist Joint Research Center Frontiers Science Center for Materiobiology and Dynamic Chemistry East China University of Science and Technology Shanghai China
2. School of Biomedical Engineering State Key Laboratory of Oncogenes and Related Genes Renji Hospital Shanghai Jiao Tong University Shanghai China
Abstract
AbstractThe development of efficient aggregation‐induced emission (AIE) active probes is crucial for disease diagnosis, particularly for tumors and cardiovascular diseases. Current AIE‐active probes primarily focus on improving their water solubility to resist aggregation, thereby achieving an initial fluorescence‐off state. However, the complex biological environment can cause undesirable aggregation, resulting in false signals. To address this issue, we have ingeniously introduced an azo group into the AIE luminogen (AIEgen), developing a reductase‐activated AIE probe, Azo‐quinoline‐malononitrile (QM)‐PN, for imaging hypoxic environments. In this probe, the azo group promotes intramolecular motion through rapid E/Z isomerization, causing the excited state energy to dissipate via non‐radiative decay, thus turning off the initial fluorescence. In the presence of reductase, Azo‐QM‐PN is reduced and cleaved to produce the hydrophobic AIEgen NH2‐QM‐PN, which subsequently aggregates and generates an in situ AIE signal, thereby imaging the hypoxic environment with reductase. Encapsulation of Azo‐QM‐PN with DSPE‐PEG2000 results in the formation of the nanoprobe Azo‐QM‐PN NPs, which can effectively penetrate cell membranes, specifically illuminate tumor cells, monitor fluctuations in azo reductase levels, and deeply penetrate and image multicellular tumor spheroids, demonstrating potential for hypoxic tumor imaging. Additionally, the nanoprobe Azo‐QM‐PN NPs can selectively image hypoxic atherosclerotic plaque tissues, showing potential for detecting atherosclerosis. Therefore, in this study, we successfully developed an enzyme‐activated AIE probe for imaging hypoxic environments, laying the foundation for further clinical applications.