Near-Infrared Emitting Polymer Nanogels for Efficient Sentinel Lymph Node Mapping

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• 作者：Young-Woock Noh ; Seong-Ho Kong ; Doo-Yeol Choi ; Hye Sun Park ; Han-Kwang Yang ; Hyuk-Joon Lee ; Hee Chan Kim ; Keon Wook Kang ; Moon-Hee Sung ; Yong Taik Lim
• 刊名：ACS Nano
• 出版年：2012
• 出版时间：September 25, 2012
• 年：2012
• 卷：6
• 期：9
• 页码：7820-7831
• 全文大小：808K
• 年卷期：v.6,no.9(September 25, 2012)
• ISSN：1936-086X

文摘

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.

Keywords:

polymer nanogel; nanoprobe; sentinel lymph node; NIR optical imaging; cancer