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Bioorthogonal Chemical Imaging of Cell Metabolism Regulated by Aromatic Amino Acids

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Bioorthogonal Molecular Turn-On Optical Imaging and Therapy.

Xinzhu Wang¹, Donghao Li¹, Kanyi Pu^1,2

¹School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, Singapore 637457, Singapore.

Chemical Reviews

|January 7, 2026

Summary

Bioorthogonal turn-on optical probes (BioTOPs) enable precise molecular imaging and therapy by activating signals through selective reactions. This technology offers high-contrast visualization and targeted interventions for diagnostics and disease treatment.

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Area of Science:

Chemical Biology
Molecular Imaging
Bioorganic Chemistry

Background:

Bioorthogonal chemistry has advanced molecular imaging and therapy over two decades.
Bioorthogonal turn-on optical probes (BioTOPs) integrate bioorthogonal handles with imaging agents for signal activation.
BioTOPs enable high-contrast, real-time visualization of biomolecules and targeted therapy with minimal off-target effects.

Purpose of the Study:

To review recent advances in the design and application of BioTOPs.
To discuss the two-step pretargeted strategy for bioorthogonal turn-on optical imaging.
To categorize bioorthogonal reactions and signal activation mechanisms used in BioTOPs.

Main Methods:

Categorization of employed bioorthogonal reactions (e.g., Staudinger ligation, cycloadditions, metal-catalyzed reactions).
Discussion of signal activation mechanisms (e.g., click-to-release, dequenching, decaging, self-assembly).
Review of design principles for integrating bioorthogonal handles with imaging agents.

Main Results:

BioTOPs leverage selective bioorthogonal reactions for signal activation, achieving high signal-to-noise ratios.
Various reaction types and activation mechanisms provide tunable kinetics and high signal turn-on folds.
The technology facilitates precise spatiotemporal control over optical signal generation.

Conclusions:

BioTOPs represent a significant innovation for molecular imaging and therapy.
Applications span biomolecule profiling, cancer diagnosis, and disease-specific interventions.
This technology holds transformative potential for molecular diagnostics and personalized medicine.