Accurate diagnosis and therapy are challenging because most diseases lack a single biomarker that distinguishes them from other disorders. A solution would enhance targeting accuracy by using AND-gated combinations of two disease-associated stimuli. Here, we report a novel “AND” molecular logic gate, enabling a double-controlled release of intact functional molecules. Benefiting from a significant difference in intramolecular cyclization rate, cargo release occurs notably faster with the presence of both stimuli. According to this finding, several AND logic probes have been developed that respond to a broad scope of stimuli and show remarkably improved signal-to-background contrast compared to those of monoresponsive probes. In addition, an AND logic probe that is responsive to monoamine oxidase (MAO) and leucine aminopeptidase (LAP) has been constructed for hepatopathy diagnosis. It works efficiently in living cells and mouse models. Of note, this probe can successfully differentiate cirrhotic from hepatitis B by testing the blood samples from patients.

中文翻译：

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开发“AND”逻辑探针的分子逻辑门及其在肝病鉴别中的应用

准确的诊断和治疗具有挑战性，因为大多数疾病缺乏将它们与其他疾病区分开来的单一生物标志物。一种解决方案将通过使用两种疾病相关刺激的 AND 门控组合来提高靶向准确性。在这里，我们报告了一种新颖的“AND”分​​子逻辑门，可以实现完整功能分子的双重控制释放。受益于分子内环化率的显着差异，在两种刺激的存在下，货物释放的速度明显更快。根据这一发现，与单响应探针相比，已开发出几种 AND 逻辑探针，它们对广泛的刺激做出响应，并显示出显着改善的信号与背景对比度。此外，一种对单胺氧化酶 (MAO) 和亮氨酸氨基肽酶 (LAP) 有反应的 AND 逻辑探针已被构建用于肝病诊断。它在活细胞和小鼠模型中有效。值得注意的是，该探针可以通过检测患者的血液样本成功区分肝硬化和乙型肝炎。