Dipartimento di Scienze del Farmaco, University of Piemonte Orientale, Via Bovio, 6, 28100, Novara, Italy.
IXTAL srl, Via Bovio 6, 28100, Novara, Italy.
Commun Biol. 2022 Sep 1;5(1):895. doi: 10.1038/s42003-022-03834-7.
Glioblastoma (GBM) is the most aggressive primary brain tumour for which both effective treatments and efficient tools for an early-stage diagnosis are lacking. Herein, we present curcumin-based fluorescent probes that are able to bind to aldehyde dehydrogenase 1A3 (ALDH1A3), an enzyme overexpressed in glioma stem cells (GSCs) and associated with stemness and invasiveness of GBM. Two compounds are selective versus ALDH1A3, without showing any appreciable interaction with other ALDH1A isoenzymes. Indeed, their fluorescent signal is detectable only in our positive controls in vitro and absent in cells that lack ALDH1A3. Remarkably, in vivo, our Probe selectively accumulate in glioblastoma cells, allowing the identification of the growing tumour mass. The significant specificity of our compounds is the necessary premise for their further development into glioblastoma cells detecting probes to be possibly used during neurosurgical operations.
胶质母细胞瘤（GBM）是最具侵袭性的原发性脑肿瘤，目前缺乏有效的治疗方法和早期诊断的有效工具。在此，我们提出了基于姜黄素的荧光探针，它能够与醛脱氢酶 1A3（ALDH1A3）结合，ALDH1A3 在神经胶质瘤干细胞（GSCs）中过度表达，与 GBM 的干性和侵袭性相关。两种化合物对 ALDH1A3 具有选择性，与其他 ALDH1A 同工酶没有明显的相互作用。事实上，它们的荧光信号只能在我们体外的阳性对照中检测到，而在缺乏 ALDH1A3 的细胞中则检测不到。值得注意的是，在体内，我们的探针选择性地聚集在胶质母细胞瘤细胞中，从而能够识别正在生长的肿瘤。我们化合物的显著特异性是将其进一步开发为神经外科手术中可能使用的胶质母细胞瘤细胞检测探针的必要前提。
