Fluorescent Probes for Enzyme Activity Imaging in Cancer and Liver Diseases

Fluorescent probes that respond to specific enzymatic activities have emerged as powerful tools in the diagnosis, monitoring and surgical guidance of cancer and liver diseases. By coupling enzyme-sensitive linkers or recognition motifs to environment-sensitive fluorophores, these probes remain non-emissive until they encounter their target enzyme, triggering a chemical transformation that restores or enhances fluorescence. Advances in probe design have prioritised near-infrared emission to minimise tissue autofluorescence and maximise penetration depth, the incorporation of peptide ligands or nanocarriers for selective delivery, and the use of molecular-logic architectures to require multiple enzyme inputs for activation. Collectively, these strategies enable real-time visualisation of proteases, aminopeptidases, oxidases and transferases involved in tumour progression, drug resistance and hepatopathy, with growing applications in early detection, therapeutic evaluation and intraoperative delineation of pathological tissue.

Research from Nature Portfolio

Recent work has delivered far-red/near-infrared fluorescence light-up probes that target specific tumour-associated proteins, achieving high-contrast imaging of malignant tissues in vitro and in vivo. These small-molecule probes employ peptide-based targeting ligands conjugated to environment-sensitive fluorogens, which remain quenched in healthy tissue but switch on upon binding to lysosomal membrane biomarker proteins in cancer cells. In murine tumour models, the probes have demonstrated selective accumulation and strong signal amplification at tumour sites, underscoring their potential for intraoperative guidance and precise biomarker quantification in oncology.

Fluorescent Probes for Enzyme Activity Imaging in Cancer and Liver Diseases publication trend

The graph below shows the total number of articles in fluorescent probes for enzyme activity imaging in cancer and liver diseases across all publications each year (not limited to Nature Index journals).

Technical terms

Fluorogenic probe: A non-fluorescent or weakly fluorescent molecule that emits a strong signal upon interaction with a specific target or environment.

Near-infrared (NIR): Electromagnetic radiation with wavelengths from approximately 650 to 900 nm, used to minimise tissue autofluorescence and enhance imaging depth.

Activatable probe: A fluorogenic probe designed to respond to a biological stimulus, such as enzyme activity, by undergoing a chemical transformation that restores or enhances fluorescence.

AND gate: A molecular design requiring two simultaneous inputs—typically two distinct enzymatic activities—to trigger signal generation and increase specificity.

Peptide ligand: A short amino acid sequence that binds selectively to a target protein, used to confer specificity to imaging probes.

References

1. Far-red/near-infrared fluorescence light-up probes for specific in vitro and in vivo imaging of a tumour-related protein. Scientific Reports (2016).
2. In vivo imaging of leucine aminopeptidase activity in drug-induced liver injury and liver cancer via a near-infrared fluorescent probe. Chemical Science (2017).
3. A Molecular Logic Gate for Developing “AND” Logic Probes and the Application in Hepatopathy Differentiation. ACS Central Science (2022).
4. A molecular-logic gate for COX-2 and NAT based on conformational and structural changes: visualizing the progression of liver disease. Chemical Science (2020).