Lysosome-specific sensing and imaging of pH variations in vitro and in vivo utilizing a near-infrared boron complex

Abstract

As a focus issue, the study of lysosomal pH has attracted much attention as it is closely associated with the state of lysosome, which plays a vital role in endocytosis and autophagy. In order to investigate the lysosomal pH, fluorescence bioimaging is one of the most widely-explored approaches. Unfortunately, the probes are insufficient to absorb or emit in the near-infrared (NIR) region, which could minimize photodamage to organisms and maximize tissue penetration in living systems. As a novel family of NIR dyes, hemicyanine has been selected for NIR bioimaging and biosensing owing to its excellent optical properties, easy preparation and good biocompatibility. Employing a classic rhodamine–hemicyanine hybrid, we first designed and synthesized a NIR boron complex (HCy-BIZ-BF₂) with lysosome-targeting and pH-sensing properties. It is worth mentioning that after HCy-BIZ was coordinated with boron fluoride, HCy-BIZ-BF₂ exhibited an improved photostability as well as an enlarged Stokes shift, and was subsequently applied to monitor the lysosomal pH in cells stimulated with chloroquine. Further investigation of pH changes in mice illustrated that HCy-BIZ-BF₂ performed well in detecting the pH in living organisms. Therefore, this concept of boron complex derived from hemicyanine is not only applicable in pH detection, but also conducive for preparing promising novel NIR bioprobes and obtaining precise measurements of physiological parameters in specific physiological processes.