Chemiluminescent Probes in Molecular Imaging

Chemiluminescent probes harness light emitted from chemical reactions to visualise biological processes without the need for external illumination. This modality offers inherently low background signals, deep tissue penetration and high sensitivity, making it attractive for in vivo molecular imaging. Core designs include 1,2-dioxetane scaffolds that undergo rapid chemiexcitation upon enzymatic or chemical activation, and afterglow nanoparticles that store and slowly release light over extended periods. Activatable probes can be tailored to respond selectively to biomarkers such as gasotransmitters, reactive oxygen species or proteolytic enzymes, while ratiometric formats enable quantitative readouts by comparing two emission wavelengths. Advances in near-infrared (NIR) chemiluminescence and biodegradable nanocarriers have addressed prior limitations of tissue penetration and biocompatibility. Collectively, these strategies have broadened the toolkit for non-invasive imaging of tumour microenvironments, enzyme activity, immune cell function and therapeutic responses, underpinning a new era of precision diagnostics and guided interventions.

Research from Nature Portfolio

Recent studies have described a ratiometric afterglow nanoplatform capable of reliable quantification of specific analytes in vivo. By integrating two chemiluminescent emitters within a single nanoparticle, the system corrects for signal attenuation and instrumental variability, achieving signal-to-background ratios of over a thousandfold for nitric oxide detection in tumours. Another report has optimised H₂S-activatable NIR afterglow probes by combining an organic electrochromic material with a photosensitiser, affording rapid turn-on kinetics and high specificity in blood and tumour models. These designs permit non-invasive delineation of small orthotopic tumours and ex vivo guidance of surgical margins. Such innovations underscore the progression from simple light-on probes towards multifunctional, quantifiable platforms with clinical potential.

Chemiluminescent Probes in Molecular Imaging publication trend

The graph below shows the total number of articles in chemiluminescent probes in molecular imaging across all publications each year (not limited to Nature Index journals).

Technical terms

Chemiluminescence: Light emission resulting from a chemical reaction, without external excitation.

Afterglow luminescence: Persistent emission of light after cessation of excitation or initial reaction, enabling delayed imaging.

Activatable probe: A sensor that remains dark until it interacts with a specific biological stimulus, yielding a turn-on signal.

Signal-to-background ratio: The intensity of emitted signal relative to background noise, indicating detection sensitivity.

Ratiometric imaging: A quantitative method comparing emissions at two wavelengths to correct for external variables.

1,2-Dioxetane: A four-membered peroxide ring that decomposes to produce chemiluminescence upon cleavage.

References

1. Stimuli‐responsive linkers and their application in molecular imaging. Exploration (2024).
2. A generic approach towards afterglow luminescent nanoparticles for ultrasensitive in vivo imaging. Nature Communications (2019).
3. Ratiometric afterglow luminescent nanoplatform enables reliable quantification and molecular imaging. Nature Communications (2022).
4. H2S-activatable near-infrared afterglow luminescent probes for sensitive molecular imaging in vivo. Nature Communications (2020).
5. A Functional Chemiluminescent Probe for in Vivo Imaging of Natural Killer Cell Activity Against Tumours. Angewandte Chemie International Edition (2021).
6. Rapid chemiexcitation of phenoxy-dioxetane luminophores yields ultrasensitive chemiluminescence assays. Chemical Science (2019).