Biocompatible Croconaine Aggregates with Strong 1.2–1.3 μm Absorption for NIR-IIa Photoacoustic Imaging in Vivo

Although photoacoustic imaging (PAI) in the second near-infrared (NIR-II) region (1.0-1.7 μm) is admired for deeper penetration and higher contrast, few organic NIR-II absorbers are available as exogenous contrast agents in vivo. A1094 belongs to the very few ∼1.1 μm absorbing croconaine dyes that have superior extinction coefficient and tend to form irregular aggregation. In this study, shape-controlled A1094@DSPE-PEG2000 micelles with a J-aggregate core with remarkable 1.2-1.3 μm absorption are fabricated as biocompatible organic agents. Excellent capabilities in photothermal conversion, photostability, and PAI are found in in vitro studies. In vivo PAI of inguinal lymph nodes and in situ glioma pre- and post-resection, all demonstrate high lymph/tumor-targeting efficiency. An ∼4.54 mm deep brain lesion is imaged at 1200 nm with minimized background and increased contrast compared to 970 nm. Overall, we achieved significant bathochromic shift of organic absorbers and expanded their PAI application to the long-wavelength end of the NIR-IIa region.