Harnessing Intermolecular Interactions to Boost Near-Infrared-II Fluorescence of Diketopyrrolopyrrole Nanoaggregates for In Vivo Imaging

Abstract Near-infrared (NIR)-II dyes hold tremendous potential for biomedical imaging and clinical applications. Structural modulation of fluorescent dyes has been widely recognized as a general approach to achieve NIR-II fluorescence. However, this strategy is often hindered by complex synthetic procedures and the obtained NIR-II dyes commonly suffer from aggregation-caused quenching. Herein, by rationally modulating intermolecular interactions, we facilely constructed two diketopyrrolopyrrole-based fluorescent dyes (DPP-2ANXF and DPP-2BTANXF) with NIR-II aggregate-state emissions. Compared with DPP-2ANXF, DPP-2BTANXF engineered with a stronger acceptor moiety showed intense red-shifted fluorescence of 970 nm with a quantum yield (QY) of 4.28% in low-polarity solution. Moreover, DPP-2BTANXF displayed strong NIR-II solid-state fluorescence with an emission peak at up to 1175 nm. Powder X-ray diffraction (PXRD) analysis and theoretical calculations revealed that the aggregated dimeric units are stabilized by multiple intermolecular interactions, leading to a narrowed energy gap. Through nanoprecipitation, DPP-2BTANXF was formulated into water-soluble nanoparticles (NPs) with NIR-I absorption and NIR-II emission (1108 nm) exhibiting a QY of 0.62%. DPP-2BTANXF NPs enabled high-contrast in vivo NIR-II fluorescence and photoacoustic imaging of mouse blood vessels, as well as imaging-guided surgical navigation of mouse tumor. Overall, this work provides an alternative strategy for developing versatile NIR-II fluorescent dyes for biomedical applications via rational modulation of intermolecular interactions.