Molecular engineering of a commercially available NIR-II fluorescent cyanine dye for improved tumor targeting and imaging

Second near-infrared window (NIR-II) fluorescence imaging has shown great promise in cancer imaging. Among the numerous NIR-II fluorescence probes, cyanine dyes have shown potential in clinical translation and attracted more and more attention. However, most commercially available NIR-II fluorescent cyanine dyes are not suitable for cancer imaging due to their low tumor targeting capability. Herein, we report an arginylglycylaspartic acid (RGD)-conjugated cyanine dye (IR806-RGD) for NIR-II fluorescence imaging of tumors. IR806-RGD is synthesized via conjugation of RGD onto the commercially available cyanine dye IR806 with three steps. Compared with IR806, IR806-RGD has a longer emission wavelength, higher NIR-II fluorescence intensity and better tumor targeting capability. In vivo tumor imaging study demonstrates that IR806-RGD can be applied for both NIR-II fluorescence and photoacoustic (PA) imaging and has a better imaging efficacy than IR806. Our work provides an approach for modification of cyanine dyes to simultaneously improve their NIR-II fluorescence signal and tumor targeting capability.