Carbazole Engineering in D-A-D Molecules to Improve the NIR-II Performance for Tumor Micrometastasis Imaging.

Abstract

It is important to image tumor micrometastases in fluorescence-guided surgery (FGS), which requires highly emissive materials with a high signal-to-background ratio. As one type of bright NIR-II dye, donor-acceptor-donor (D-A-D) molecules have been widely applied for in vivo imaging. However, the brightness of D-A-D molecules when encapsulated in nanoparticles for bioimaging is often unsatisfactory due to aggregation-caused quenching or a decrease in absorption. In this study, we introduced carbazole groups in the D-A-D molecules, which resulted in a reduction of fluorescence quenching in the aggregated state due to the larger intermolecular distance. Through proper engineering of the carbazole groups, the emission spectra of the nanoparticles could be red-shifted with a peak beyond 1000 nm, while maintaining strong absorption and high quantum yield. The brightest <b>TBTC-4</b> nanoparticles were successfully applied for tumor micrometastasis imaging in mice, with metastases as small as 0.5 mm diameter, which demonstrates their promising clinical application in FGS.