Photoacoustic Imaging with Nanoparticle Probes and Contrast Agents

Photoacoustic imaging (PAI) harnesses the photoacoustic effect by coupling pulsed optical excitation with ultrasonic detection to achieve high spatial resolution at clinically relevant depths. The introduction of nanoparticle probes and contrast agents has transformed PAI from an anatomical modality into a molecular and functional imaging platform. Nanometre-scale constructs—including plasmonic gold, carbon-based and organic dye-loaded carriers—enhance optical absorption in the near-infrared (NIR) window, improving penetration depth and specificity. Tailoring surface chemistry with targeting ligands or stimuli-responsive moieties has enabled selective accumulation and activatable signal generation in response to biomarkers such as pH, hypoxia and reactive oxygen species. Supramolecular assemblies and hybrid nanoparticles further refine multispectral capabilities, allowing simultaneous quantification of multiple analytes. These advances underpin applications from cancer diagnosis and therapy guidance to monitoring of physiological processes in preclinical and translational settings. By integrating with conventional ultrasound, optical coherence tomography or magnetic resonance imaging, nanoparticle-based PAI platforms promise comprehensive structural, functional and molecular information for early diagnosis and personalised medicine.

Research from Nature Portfolio

Recent studies have demonstrated the power of supramolecular host–guest chemistry to amplify PAI contrast. Assemblies based on cucurbit[8]uril inclusion of xanthene-derivative chromophores show red-shifted absorption and quenched fluorescence, boosting optoacoustic signal for multispectral tumour imaging in vivo. This strategy highlights the potential of tailored supramolecular nanostructures to overcome solubility and extinction coefficient limitations of small-molecule agents. Another recent innovation employs a diene electrochromic chromophore optimised for hydroxyl radical responsiveness, yielding ratiometric near-infrared fluorescence and photoacoustic readouts that track reactive oxygen species generation in tumours undergoing ferroptosis or radiotherapy. As an earlier foundational advance, a hypoxia-activated N-oxide probe has established a paradigm for enzymatically triggered contrast, where reduction under low oxygen produces a distinct absorption signature, enabling high-resolution photoacoustic detection of hypoxic tissues.

Photoacoustic Imaging with Nanoparticle Probes and Contrast Agents publication trend

The graph below shows the total number of articles in photoacoustic imaging with nanoparticle probes and contrast agents across all publications each year (not limited to Nature Index journals).

Technical terms

Photoacoustic imaging: A hybrid biomedical modality where pulsed light absorption induces ultrasonic waves for deep-tissue imaging.

Contrast agent: An exogenous material that enhances imaging signal by increasing optical absorption at specific wavelengths.

Near-infrared window: The spectral range (approximately 650–900 nm) where light penetration in tissue is maximised.

Activatable probe: A contrast agent designed to switch on or alter its signal in response to a specific biological stimulus.

Supramolecular assembly: Nanostructures formed via non-covalent interactions between host molecules and guests to tune optical properties.

Spectral unmixing: Computational separation of multiple absorbers’ photoacoustic signals based on their distinct spectra.

References

1. Multimodal optoacoustic imaging: methods and contrast materials. Chemical Society Reviews (2024).
2. Renally Clearable Ultraminiature Chain‐Like Gold Nanoparticle Clusters for Multimodal Molecular Imaging of Choroidal Neovascularization. Advanced Materials (2023).
3. Cucurbit[8]uril-based water-dispersible assemblies with enhanced optoacoustic performance for multispectral optoacoustic imaging. Nature Communications (2023).
4. A bioreducible N-oxide-based probe for photoacoustic imaging of hypoxia. Nature Communications (2017).
5. Generation of hydroxyl radical-activatable ratiometric near-infrared bimodal probes for early monitoring of tumor response to therapy. Nature Communications (2021).