Azide-Dye Unexpected Bone Targeting for Near-Infrared Window II Osteoporosis Imaging

Abstract

Azide is an important chemical functional group and has been widely used in chemical biology. However, the impact of azide on the <i>in vivo</i> behaviors of compounds has been rarely studied. Herein, azide was introduced into a fluorescent dye for the near-infrared window two (NIR-II) bone imaging. Specifically, we designed and synthesized the small-molecule NIR-II dyes, N₃-FEP-4T capped with azide and FEP-4T without azide capping. <i>In vitro</i> assays revealed that N₃-FEP-4T showed 5- and 5.6- times higher hydroxyapatite accumulation and macrophage uptake than those of FEP-4T, respectively. Moreover, N₃-FEP-4T displayed higher bone uptakes and much better bone NIR-II imaging quality, demonstrating the specific bone-targeting ability of the azide-containing probe. N₃-FEP-4T was then further successfully used for osteoporosis NIR-II imaging. Overall, our study provides insights into the impact of azide on the <i>in vivo</i> behavior of azide-containing compounds and opens a new window for biological application of azide.