title: Near-infrared emitting polymer nanogels for efficient sentinel lymph node mapping.
abstract: 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.
authors.affiliation: Graduate School and Department of Analytical Science and Technology, Chungnam National University, Daejeon 305-764, South Korea.
authors.forename: Young-Woock
authors.initials: YW
authors.lastname: Noh
authors.forename: Seong-Ho
authors.initials: SH
authors.lastname: Kong
authors.forename: Doo-Yeol
authors.initials: DY
authors.lastname: Choi
authors.forename: Hye Sun
authors.initials: HS
authors.lastname: Park
authors.forename: Han-Kwang
authors.initials: HK
authors.lastname: Yang
authors.forename: Hyuk-Joon
authors.initials: HJ
authors.lastname: Lee
authors.forename: Hee Chan
authors.initials: HC
authors.lastname: Kim
authors.forename: Keon Wook
authors.initials: KW
authors.lastname: Kang
authors.forename: Moon-Hee
authors.initials: MH
authors.lastname: Sung
authors.forename: Yong Taik
authors.initials: YT
authors.lastname: Lim
mesh_terms: D000818:Animals; D005456:Fluorescent Dyes; D005782:Gels / Q000737:chemistry; D007259:Infrared Rays; D008198:Lymph Nodes / Q000166:cytology*; D051379:Mice; D008856:Microscopy, Fluorescence / Q000379:methods*; D053769:Nanocapsules / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D021701:Sentinel Lymph Node Biopsy / Q000379:methods; D013552:Swine
chemical_list: D005456:Fluorescent Dyes; D005782:Gels; D053769:Nanocapsules; D011108:Polymers