A Molecular Logic Gate for Developing AND Logic Probes and the Application in Hepatopathy Differentiation

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 diseaseassociated 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 intrawith 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-tobackground 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.

Automated summary

This study reports a novel molecular logic gate that enables a double-controlled release of intact functional molecules by combining two disease-associated stimuli. Compared to traditional monoresponsive probes, these AND logic probes show significantly improved signal-to-background contrast and have been successfully used in hepatopathy diagnosis.