A Zirconium Aza-BODIPY Derivative as a Near-Infrared Fluorescent/Photoacoustic Imaging Bimodal Probe

Aza-boron-dipyrromethenes (aza-BODIPYs) are established fluorescent imaging agents derived from aza-DIPY ligands coordinated to boron. While many modifications of the aza-DIPY core have optimized the photophysical properties, replacing boron with a metal ion remains underexplored. Here, we report four zirconium-based aza-DIPY complexes (aza-ZrDIPYs) and show that this substitution enables bimodal NIR-I fluorescence and photoacoustic imaging. The complexes were fully characterized and evaluated photophysiologically. The bromo derivative, aza-ZrDIPY-Br, displayed particularly favorable dual-mode properties. It showed low in vitro cytotoxicity and an effective uptake in two human cell lines. In mice bearing subcutaneous U87-MG glioblastoma tumors, intravenous or peritumoral administration led to passive tumor accumulation, with tumor-to-background ratios of up to 5 (photoacoustic) and 2 (optical). These results highlight aza-ZrDIPY-Br as a promising bimodal probe for tumor imaging, with future work aimed at improving specificity through active targeting.