Analyte-Induced p-Tunable Hemicyanine Dual-Locked Molecular Platform for Tumor Precision Imaging.

Dual-locked probes that precisely visualize the tumor microenvironment (TME) are poised to close a critical detection gap in personalized medicine. However, traditional dual-locked systems are still constrained by sluggish response kinetics, low sensitivity, intricate design, and limited generality. To overcome these challenges, we introduce a general "analyte-induced p-tunable" () hemicyanine dual-locked platform () for tumor precision imaging. Interestingly, the p of can be readily modulated by adjusting the electron-donating ability of the optically tunable site. Leveraging this feature, the analyte response alters the electron-donating capacity of the recognition unit, shifting the probe's p and enabling simultaneous detection of both acidity and the other biomarker. To validate the versatility of , we devised two dual-locked probes (p = 5.4) and (p = 4.9), bearing acetyl (for carboxylesterase) and acrylate moiety (for Cys) recognition units that are cleaved to release (p = 6.6) , concomitantly activating a pH response that elicits robust fluorescence enhancement. These two probes demonstrated rapid, specific, and sensitive response and high tumor-to-normal tissue ratios for hepatocellular carcinoma screening and imaging. Thus, the strategy establishes a generalizable dual-locked platform for next-generation dual-locked probes, offering a highly promising tool for intraoperative navigation and precision tumor imaging.