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AND-Logic-Based Dual-Lock Hemicyanine Fluorescence Probe for Accurate Hypoxia Assessment in Tumors
Yurong Liu1,2, Yaru Wang1, Wei Sun1
1Marshall Laboratory of Biomedical Engineering, International Cancer Center, Laboratory of Evolutionary Theranostics (LET), School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen University, Shenzhen 518055, China.
None:
The hypoxia tumor microenvironment (TME) critically influences treatment efficacy, driving a significant demand for real-time in vivo hypoxia assessment. However, conventional single-stimulus responsive probes suffer from insufficient imaging precision. To address this, we developed a new AND-logic-based pH/nitroreductase (NTR) dual-lock hemicyanine, namely LET-16, for accurate hypoxia assessment in tumors. LET-16 responds to acidic TME, forming a positively charged open-ring structure that enhances cell entry. Inside tumor cells, it reacts with overexpressed NTR, thus emitting a fluorescence signal. LET-16 demonstrates excellent dual-responsive activation both in vitro and in vivo, enabling precise imaging of tumor hypoxia. This work not only provides a robust tool for accurate hypoxia assessment but also offers a strategy for engineering versatile hemicyanine scaffolds adaptable to complex diagnostic needs, such as multianalyte detection and advanced logic-gate responses.
