Novel bright-emission small-molecule NIR-II fluorophores for in vivo tumor imaging and image-guided surgery

Though high brightness and biocompatible small NIR-II dyes are highly desirable in clinical or translational cancer research, their fluorescent cores are relatively limited and their synthetic processes are somewhat complicated. Herein, we have explored the design and synthesis of novel NIR-II fluorescent materials (<b>H1</b>) without tedious chromatographic isolation with improved fluorescence performance (QY ≈ 2%) by introducing 2-amino 9,9-dialkyl-substituted fluorene as a donor into the backbone. Several types of water-soluble and biocompatible NIR-II probes: <b>SXH</b>, <b>SDH</b>, and <b>H1 NPs</b> were constructed <i>via</i> different chemical strategies based on <b>H1</b>, and then their potential to be used in <i>in vivo</i> tumor imaging and image-guided surgery in the NIR-II region was explored. High levels of uptake were obtained for both passive and active tumor targeting probes <b>SXH</b> and <b>SDH</b>. Furthermore, high resolution imaging of blood vessels on tumors and the whole body of living mice using <b>H1 NPs</b> for the first time has demonstrated precise NIR-II image-guided sentinel lymph node (SLN) surgery.