Université Grenoble Alpes, INSERM U1209, CNRS UMR 5309, Institute for Advanced Biosciences (IAB), Grenoble 38000, France.
Institut de Chimie Moléculaire de l'Université de Bourgogne, Université de Bourgogne, CNRS UMR 6302, Dijon 21078, France.
J Med Chem. 2024 Sep 26;67(18):16635-16648. doi: 10.1021/acs.jmedchem.4c01435. Epub 2024 Sep 17.
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 was observed across different tumor cells. , the distribution and safety profiles were determined, and tumor uptake was assessed in various tumor types. Following intravenous injection, 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.
Aza-BODIPYs 是一类荧光团，其π共轭体系通过硼原子得到刚性和稳定化。增强其荧光性质的一种有前途的策略是用金属离子取代硼原子。在这里，我们描述了一种水溶性衍生物的合成和表征，其中金属是镓 (III) 离子，称为 WazaGaY（水溶性 aza-GaDIPY）。通过两个铵取代基确保了水溶性，与二甲基氨基类似物相比，其发生了红移并显著提高了量子产率。观察了 的不同肿瘤细胞中的细胞行为。还确定了分布和安全性特征，并在各种肿瘤类型中评估了肿瘤摄取。静脉注射后，即使没有特异性缀合，也能使皮下植入的小鼠肿瘤与肌肉的比率（范围从 7 到 20）清晰区分，甚至能区分。其作为荧光引导手术的造影剂的潜力得到了证实。
