Water‐Soluble Lipophilic Near‐Infrared Region II Fluorophores for High‐Brightness Lipid Layer and Lipid Droplets Imaging Applications

Abstract

Fluorescence imaging in the second near‐infrared region (NIR‐II, 1000–1700 nm) has garnered considerable attention for displaying the biological information of deep tissues. However, the lack of biocompatible contrast agents with bright NIR‐II emission has hampered the precise clinical application of deep tissue imaging. Here, a lipophilic enhancement strategy employing donor‐acceptor‐donor (D‐A‐D) molecules, introducing long alkoxy chains and quaternary ammonium salts for the development of highly bright water‐soluble NIR‐II fluorophores (BBTD‐2C‐N), is described. Notably, liposome‐encapsulated BBTD‐2C‐N nanoparticles (B‐2C‐N/DMPC) in aqueous solution exhibit a 1.8‐fold increase in NIR‐II fluorescence brightness compared to free BBTD‐2C‐N in methanol. Avoidance of the aggregation‐caused quenching effect and enhanced NIR‐II fluorescence are attributed to significantly attenuated π–π stacking interactions and maintained monodisperses in the hydrophobic liposome shell. Moreover, BBTD‐2C‐N demonstrates superior performance in visualizing lipid droplet‐rich HeLa cells in vitro, as well as precise monitoring of adipose tissue and fatty liver in vivo. This study reveals a new avenue for the development of bright NIR‐II fluorophores and precise in vivo imaging.