NIR-II Fluorophores for Biomedical Imaging and Theranostics

The second near-infrared window (NIR-II; 1000–1700 nm) has emerged as a transformative platform for in vivo optical imaging and integrated therapy. By operating at longer wavelengths than conventional visible or first near-infrared probes, NIR-II fluorophores benefit from deeper tissue penetration, reduced light scattering and minimal autofluorescence, thereby delivering high spatial resolution and excellent signal-to-background contrast. A diverse suite of NIR-II agents has been developed, encompassing small-molecule organic dyes, semiconducting polymer nanoparticles, inorganic nanocrystals and supramolecular dye–protein complexes. Rational molecular design—through donor–acceptor motifs, rigidified backbones or self-assembly—has enhanced brightness, photostability and aqueous compatibility, while bioconjugation strategies have enabled precise targeting of tumours, vasculature and subcellular compartments. Coupled with advances in excitation sources and detection systems, these fluorophores underpin a new generation of image-guided surgery, real-time vascular mapping, lymph node tracing and stimulus-responsive theranostics. The global significance of NIR-II technology lies in its potential to improve diagnostic accuracy, reduce operative time, personalise treatment monitoring and ultimately accelerate clinical translation across oncology, cardiovascular surgery and regenerative medicine.

Research from Nature Portfolio

Seminal work on supramolecular enhancement has demonstrated that assembly of a sulfonated organic dye within a protein scaffold can boost fluorescence by over two orders of magnitude. This bright molecular complex achieved the highest recorded quantum yield for a small-molecule NIR-II agent in aqueous solution, enabling video-rate cardiac imaging, deep lymph node visualisation and clear delineation of microvascular structures at 50 frames per second. Building on donor–acceptor chemistry, a series of thiopyrylium-based fluorophores were engineered to exhibit frequency upconversion luminescence upon near-infrared excitation. These dyes not only deliver sharp NIR-II emission for live-cell and in vivo tumour imaging with subcellular resolution at nanomolar concentrations, but also convert absorbed light into heat for targeted photothermal therapy. Together, these studies establish a dual-function paradigm in which diagnostic imaging and on-demand therapy are synchronised without the need for external photosensitisers or reactive oxygen species.

NIR-II Fluorophores for Biomedical Imaging and Theranostics publication trend

The graph below shows the total number of articles in nir-ii fluorophores for biomedical imaging and theranostics across all publications each year (not limited to Nature Index journals).

Technical terms

NIR-II window: The second near-infrared spectral region (1000–1700 nm) offering reduced scattering and autofluorescence for deep-tissue optical imaging.

Quantum yield: A measure of fluorescence efficiency, defined as the ratio of emitted photons to absorbed photons.

Theranostics: The integration of diagnostic imaging and therapeutic functions within a single molecular or nanoscale agent.

Donor–acceptor architecture: A molecular design featuring electron-donating and electron-accepting units to tailor absorption and emission properties.

Frequency upconversion luminescence: An anti-Stokes process in which lower-energy photons are absorbed and higher-energy photons are emitted, enabling bright fluorescence under near-infrared excitation.

References

1. Rational Design of a Self‐Assembling High Performance Organic Nanofluorophore for Intraoperative NIR‐II Image‐Guided Tumor Resection of Oral Cancer. Advanced Science (2023).
2. A high quantum yield molecule-protein complex fluorophore for near-infrared II imaging. Nature Communications (2017).
3. Upconversion NIR-II fluorophores for mitochondria-targeted cancer imaging and photothermal therapy. Nature Communications (2020).
4. A thiopyrylium salt for PET/NIR‐II tumor imaging and image‐guided surgery. Molecular Oncology (2020).
5. Diketopyrrolopyrrole-based semiconducting polymer nanoparticles for in vivo second near-infrared window imaging and image-guided tumor surgery. Chemical Science (2018).