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用于靶向全淋巴结的多价甘露糖修饰近红外纳米探针。

Multivalent Mannose-Decorated NIR Nanoprobes for Targeting Pan Lymph Nodes.

作者信息

Wada Hideyuki, Hyun Hoon, Bao Kai, Lee Jeong Heon, El Fakhri Georges, Choi Yongdoo, Choi Hak Soo

机构信息

Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.

Department of Gastroenterological Surgery II, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.

出版信息

Chem Eng J. 2018 May 15;340:51-57. doi: 10.1016/j.cej.2018.01.008. Epub 2018 Jan 3.

Abstract

Lymphadenectomy is a prerequisite for most malignancies to define the precise staging of cancer, as well as resect the possible metastases completely. While it improves prognosis, lymphadenectomy often causes postoperative edema or bleeding because of unclear surgical margins. In this study, we synthesized near-infrared (NIR) fluorescent nanoprobes with conjugating various mannose moieties on the surface to target macrophages in the lymph node. Armed with these NIR nanoprobes, we demonstrated the feasibility of intraoperative pan lymph nodes (PLN) mapping and real-time optical imaging under the NIR fluorescence imaging system. We found that even single mannose-conjugated ZW800-1 showed specific uptake in lymph nodes within 4 h, and multiple mannose-employed polyrotaxanes highlighted PLN efficiently with low background signals in major organs. This technology can help surgeons perform lymphadenectomy with ease and safety by identifying all regional lymph nodes proficiently after a single intravenous injection of NIR nanoprobes.

摘要

淋巴结清扫术是大多数恶性肿瘤精确确定癌症分期以及完全切除可能转移灶的先决条件。虽然淋巴结清扫术可改善预后,但由于手术切缘不清晰,该手术常导致术后水肿或出血。在本研究中,我们合成了近红外(NIR)荧光纳米探针,其表面偶联了各种甘露糖部分,以靶向淋巴结中的巨噬细胞。借助这些NIR纳米探针,我们证明了在NIR荧光成像系统下进行术中全淋巴结(PLN)mapping及实时光学成像的可行性。我们发现,即使是单个甘露糖偶联的ZW800-1在4小时内也能在淋巴结中显示出特异性摄取,而多个使用甘露糖的聚轮烷能以主要器官中的低背景信号有效突出显示PLN。这项技术可通过在单次静脉注射NIR纳米探针后熟练识别所有区域淋巴结,帮助外科医生轻松、安全地进行淋巴结清扫术。

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