WazaGaY: An Innovative Aza-BODIPY-Derived Near-Infrared Fluorescent Probe for Enhanced Tumor Imaging

Aza-BODIPYs represent
a class of fluorophores in which
the π-conjugated
system is rigidified and stabilized by a boron atom. A promising strategy
to enhance their fluorescence properties involves replacing the boron
atom with a metal ion. Here, we describe the synthesis and characterization
of a water-soluble derivative where the metal is a gallium­(III) ion,
termed WazaGaY (water-soluble aza-GaDIPY). Water solubility is ensured
by two ammonium substituents, inducing a bathochromic shift and a
significant increase in quantum yield compared to that of the dimethylamino
analog. The cellular behavior of WazaGaY-1 was observed
across different tumor cells. In vivo, the distribution
and safety profiles were determined, and tumor uptake was assessed
in various tumor types. Following intravenous injection, WazaGaY-1 enabled clear discrimination of tumors engrafted subcutaneously
in mice with high tumor-to-muscle ratios (ranging from 7 to 20), even
in the absence of specific conjugation. Its potential as a contrast
agent for fluorescence-guided surgery was confirmed.