Stealth-like polysarcosine-modified nanoparticles with low dye doses and long blood circulation for efficient breast cancer pulmonary metastasis imaging.

Fluorescence imaging (FLI) in the near-infrared-II (NIR-II; 1000-1700 nm) window holds great potential for cancer metastasis imaging owing to its deep tissue penetration and a high signal-to-background ratio. However, currently reported organic NIR-II contrast agents generally present problems such as poor water solubility, low NIR-II fluorescence quantum yield (QY), short blood circulation half-life (t1/2), high injection doses, and undesirable tumor accumulation. In this study, an NIR-II small-molecule-based polymer (TQF-PSar) modified with four dense/hydrophilic polysarcosine (PSar) arms was prepared for efficient breast cancer pulmonary metastasis imaging. The NIR-II intensity of TQF-PSar (whose QY was calculated to be 1%) was 26.4-fold higher than that of the PEGylated nanoparticles (TQF-PEG NPs) at the same low dye dose (core TQF concentration: 2.5 µg mL-1). Moreover, owing to the ideal stealth character, TQF-PSar displayed a more prolonged blood circulation t1/2 (36.9 h) and better tumor accumulation capability than TQF-PEG NPs even at this low dye concentration. Finally, the successful use of TQF-PSar in noninvasive NIR-II FLI for breast cancer pulmonary metastasis was demonstrated in living mice.