Molecular engineering of ultra-strong acidic NIR probes for real-time pharmacodynamic profiling of antacid drugs via in vivo gastric acid imaging.

Gastric acid dynamics play a pivotal role in diagnosing gastrointestinal disorders, yet conventional pH monitoring methods, including invasive endoscopy and gastric acid aspiration tests, suffer from poor patient compliance, delayed feedback, and inability to assess drug efficacy in real time. To address these limitations, we developed Si-3Py, a near-infrared (NIR) fluorescent organic small-molecule probe with ultra-acidic pH responsiveness (pKa = 2.32) and exceptional photostability. Crucially, the NIR emission of Si-3Py, coupled with its pH-responsive transition range precisely aligned with the physiological pH of gastric fluid (1.5-3.5), allow deep-tissue penetration and high signal-to-noise ratios, overcoming light attenuation challenges in gastric environments. This probe enables non-invasive, real-time in situ visualization of gastric pH fluctuations during feeding and digestion in murine models. Furthermore, we pioneered its application in evaluating the acid-suppressing capacity of antacid drugs through dynamic fluorescence signal analysis, establishing a novel platform for personalized pharmacodynamic assessment. This work bridges the gap between fundamental pH sensing and clinical translation, offering a paradigm for pain-free, high-precision gastric diagnostics and therapeutic monitoring.