Highly bright aggregation-induced emission nanodots for precise photoacoustic/NIR-II fluorescence imaging-guided resection of neuroendocrine neoplasms and sentinel lymph nodes

Owing to the complementary high spatial resolution and signal-to-noise ratio, the dual-modality imaging technique of photoacoustic imaging (PAI)/the second near-infrared window fluorescence imaging (NIR-II FI) holds great promise for the detection of tumor tissues and sentinel lymph nodes (SLNs). Herein, by developing two aggregation-induced emission luminogens (AIEgens) (C-NTBD and O-NTBD) with benzodithiadiazole as the electron acceptor, PAI/NIR-II FI was applied to the diagnosis and treatment of neuroendocrine neoplasms (NENs) and their SLNs for the first time. Both AIEgens exhibited good PAI properties as well as intense NIR-II fluorescence emission. Among them, C-NTBD nanoparticles (NPs) have better PAI and NIR-II FI performance with maximum absorption at 732 nm and emission peak at 1042 nm. In NENs-bearing nude mice model, after successful preoperative localization of NENs by PAI, NIR-II FI was then used to detect SLNs. Under the NIR-II FI guidance of C-NTBD NPs, an SLN with a diameter of 1 mm located in the chest wall and far away from the primary tumor site was even detected and precisely removed. This dual-modality imaging technology could improve the detection of NENs and the accuracy of intraoperative SLNs dissection, improve patient prognosis, and provide a new strategy for the precise treatment of NENs.