Tumor metastatic lymph node mapping has been widely used to predict the metastatic spread of primary tumor and guide the lymph node dissection in clinical practice. In this research, a new near‐infrared (NIR)‐emitting low molecular weight heparin (LMWHEP)‐modified Cy7‐loaded nanoliposome (LMWHEP‐NLips/Cy7) was developed and had the particle size of about 80 nm and the fluorescence intensity of about 2300, which is optimal for metastatic lymph node uptake and imaging. The NIR‐emitting nanoliposomes were designed by LMWHEP coating on the surface of Cy7‐loaded nanoliposome (NLips/Cy7) according to electrostatic attraction. The LMWHEP‐NLips/Cy7 with negligible cytotoxicity for Hela and RAW264.7 cells and was found to be fluorescent stability compared with the Cy7‐free dye at room temperature. The BALB/c nude mice bearing tumor lymphatic metastasis was established at eighth week post‐injection by subcutaneously injecting Hela cells suspension. Heparanase (HPA) expression concentrations quantitatively measured by ELISA kit respectively were 237.42U/mL, 214.82U/mL and 128.45U/mL in the extracellular Hela cells, metastatic popliteal and iliac lymph node. LMWHEP‐NLips/Cy7 successfully increased fluorescence signal in the metastatic lymph node compared with normal lymph node and achieve in vivo and ex vivo high fluorescence signal within 10 min and retention time up to 4 h post‐injection. Maximum mean fluorescence intensity of the LMWHEP‐NLips/Cy7 group was significantly more than NLips/Cy7 group (increase 2‐fold in the metastatic popliteal lymph node and 4.8‐fold in the metastatic iliac lymph node, p < 0.05). The experimental results demonstrating LMWHEP‐NLips/Cy7 have the potential utility as specific, biosafe and stable near‐infrared imaging contrast agents for HPA‐expression tumor metastatic lymph node mapping. Copyright © 2016 John Wiley & Sons, Ltd.

中文翻译：

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基于酶-底物相互作用的近红外发射低分子量肝素修饰的纳米脂质体对转移性淋巴结的荧光分子成像

肿瘤转移性淋巴结作图已被广泛用于预测原发性肿瘤的转移扩散，并在临床实践中指导淋巴结清扫。在这项研究中，开发了一种新的发射近红外（NIR）的低分子量肝素（LMWHEP）修饰的Cy7负载纳米脂质体（LMWHEP-NLips / Cy7），其粒径约为80 nm，荧光强度为约为2300，最适合转移性淋巴结摄取和成像。根据静电吸引，通过在载有Cy7的纳米脂质体（NLips / Cy7）表面上的LMWHEP涂层设计发射NIR的纳米脂质体。LMWHEP-NLips / Cy7对Hela和RAW264.7细胞的细胞毒性可忽略不计，并且与室温下不含Cy7的染料相比，具有荧光稳定性。通过皮下注射Hela细胞悬液，在注射后第8周建立带有肿瘤淋巴转移的BALB / c裸鼠。ELISA试剂盒定量测定的细胞外Hela细胞，转移性pop，淋巴结中乙酰肝素（HPA）的表达浓度分别为237.42U / mL，214.82U / mL和128.45U / mL。与正常淋巴结相比，LMWHEP‐NLips / Cy7成功地提高了转移淋巴结的荧光信号并达到了体内和离体高荧光信号在10分钟之内，保留时间长达注射后4小时。LMWHEP-NLips / Cy7组的最大平均荧光强度显着高于NLips / Cy7组（转移的pop腹淋巴结增加2倍，转移的淋巴结增加4.8倍，p  <0.05）。实验结果表明LMWHEP‐NLips / Cy7具有潜在的实用性，可作为特异性，生物安全和稳定的近红外成像造影剂用于HPA表达肿瘤转移性淋巴结标测。版权所有©2016 John Wiley＆Sons，Ltd.