Graduate School and Department of Analytical Science and Technology, Chungnam National University, Daejeon 305-764, South Korea.
ACS Nano. 2012 Sep 25;6(9):7820-31. doi: 10.1021/nn301949y. Epub 2012 Aug 8.
Sentinel lymph node (SLN) mapping has been widely used to predict the metastatic spread of primary tumor to regional lymph nodes in clinical practice. In this research, a new near-infrared (NIR)-emitting polymer nanogel (NIR-PNG) having a hydrodynamic diameter of about 30 nm, which is optimal for lymph node uptake, was developed. The NIR-emitting polymer nanoprobes were designed and synthesized by conjugating IRDye800 organic dye to biodegradable pullulan-cholesterol polymer nanogels. The NIR-PNG nanoprobes were found to be photostable compared with the IRDye800-free dye at room temperature. Upon intradermal injection of the NIR-PNG into the front paw of a mouse, the nanoprobes entered the lymphatic system and migrated to the axillary lymph node within 2 min. The NIR fluorescence signal intensity and retention time of NIR-PNG in the lymph node were superior to the corresponding properties of the IRDye800-free dye. A immunohistofluorescence study of the SLN resected under NIR imaging revealed that the NIR-PNG nanoprobes were predominantly co-localized with macrophages and dendritic cells. Intradermal injection of NIR-PNG nanoprobes into the thigh of a pig permitted real-time imaging of the lymphatic flow toward the SLN. The position of the SLN was identified within 1 min with the help of the NIR fluorescence images. Taken together, the experimental results demonstrating the enhanced photostability and retention time of the NIR-PNG provide strong evidence for the potential utility of these polymer probes in cancer surgery such as SLN mapping.
前哨淋巴结 (SLN) 作图已广泛用于预测原发性肿瘤向区域淋巴结的转移扩散。本研究开发了一种新的近红外 (NIR) 发射聚合物纳米凝胶 (NIR-PNG)，其水动力学直径约为 30nm，非常适合淋巴结摄取。通过将 IRDye800 有机染料缀合到可生物降解的普鲁兰-胆固醇聚合物纳米凝胶上，设计并合成了 NIR 发射聚合物纳米探针。与室温下无 IRDye800 的染料相比，NIR-PNG 纳米探针具有更好的光稳定性。将 NIR-PNG 经皮注射到小鼠前脚后，纳米探针进入淋巴管并在 2 分钟内迁移到腋窝淋巴结。NIR-PNG 在淋巴结中的荧光信号强度和保留时间优于无 IRDye800 染料的相应性质。NIR 成像下切除的 SLN 的免疫荧光研究表明，NIR-PNG 纳米探针主要与巨噬细胞和树突状细胞共定位。将 NIR-PNG 纳米探针经皮注射到猪大腿中，允许实时观察向 SLN 的淋巴流动。在 NIR 荧光图像的帮助下，可在 1 分钟内识别出 SLN 的位置。综上所述，NIR-PNG 的增强光稳定性和保留时间的实验结果为这些聚合物探针在 SLN 作图等癌症手术中的潜在应用提供了有力证据。
