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用于精准光声/NIR-II 荧光成像引导神经内分泌肿瘤和前哨淋巴结切除的高亮聚集诱导发射纳米点。

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

机构信息

Department of Geriatric Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.

State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, and College of Life Sciences, Nankai University, Tianjin, 300071, China.

出版信息

Biomaterials. 2022 Oct;289:121780. doi: 10.1016/j.biomaterials.2022.121780. Epub 2022 Sep 2.

Abstract

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.

摘要

由于具有互补的高空间分辨率和信噪比,光声成像(PAI)/近红外二区荧光成像(NIR-II FI)的双模态成像技术有望用于肿瘤组织和前哨淋巴结(SLNs)的检测。在此,通过开发两种具有苯并二噻二唑作为电子受体的聚集诱导发光体(AIEgens)(C-NTBD 和 O-NTBD),首次将 PAI/NIR-II FI 应用于神经内分泌肿瘤(NENs)及其 SLNs 的诊断和治疗。两种 AIEgens 均表现出良好的 PAI 特性和强烈的近红外二区荧光发射。其中,C-NTBD 纳米颗粒(NPs)具有更好的 PAI 和 NIR-II FI 性能,最大吸收波长为 732nm,发射峰波长为 1042nm。在携带 NENs 的裸鼠模型中,成功地通过 PAI 对 NENs 进行术前定位后,然后使用 NIR-II FI 来检测 SLNs。在 C-NTBD NPs 的 NIR-II FI 引导下,甚至可以检测到并精确切除位于胸壁且远离原发肿瘤部位的直径为 1mm 的 SLN。这种双模态成像技术可以提高 NENs 的检测和术中 SLNs 解剖的准确性,改善患者预后,并为 NENs 的精确治疗提供新策略。

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