PEGylation Regulates Self-Assembled Small-Molecule Dye-Based Probes from Single Molecule to Nanoparticle Size for Multifunctional NIR-II Bioimaging.

To date, small-molecule dye-based probes have been at the forefront of research in biomedical imaging, especially in the second near-infrared (NIR-II) window (1.0-1.7 µm). However, how to precisely regulate the synthesized size of NIR-II organic dye-based probes remains challenging. Moreover, systematic studies on whether the size of NIR-II probes affects optical/pharmacokinetic properties are still rare. Here, an ingenious PEGylation strategy is developed to regulate the self-assembly size of organic dye-based (CH1055 scaffold) NIR-II probes (SCH1-SCH4) from nanoparticles to the single molecule, and the relationship between their size and chemical/physical properties is thoroughly investigated. Based on their own merits, nanoprobe SCH1 (≈170 nm), with outstanding fluorescent brightness (quantum yield ≈0.14%), performs accurate tracing of the lymphatic system as well as identification of vessel networks in mice brains with excellent signal-to-background ratio images. Meanwhile, rapidly excreted SCH4, showing fast and high passive liver tumor uptake and promising tumor/normal tissue ratios (>7), is capable of facilitating precise image-guided tumor surgery, and also demonstrates the first example of the assessment of liver fibrosis in the NIR-II window.