Weill Cornell Medicine, Cornell University, New York, New York 10065, United States.
Memorial Sloan Kettering Cancer Center, New York, New York 10065, United States.
ACS Chem Biol. 2023 May 19;18(5):1237-1245. doi: 10.1021/acschembio.3c00156. Epub 2023 Apr 18.
Hematoxylin & eosin (H&E) is the gold standard histological stain used for medical diagnosis and has been used for over a century. Herein, we examined the near-infrared II (NIR-II) fluorescence of this stain. We observed significant NIR-II emission from the hematoxylin component of the H&E stain. We found that the emission intensity, using the common aluminum(III) hematoxylin mordant, could be modulated by the availability of endogenous iron(III), and this emission intensity increased at higher oxidative stress. Our mechanistic investigations found that hematoxylin emission reported the nuclear translocation of the iron via the protein ferritin. In human tumor tissue samples, oxidative stress biomarkers correlated with hematoxylin NIR-II emission intensity. Emission response of the stain was also observed in human Alzheimer's disease brain tissue regions affected by disease progression, suggesting that ferritin nuclear translocation is preserved in these regions as an oxidative stress response. These findings indicate that NIR-II emission from the H&E stain provides a new source of redox information in tissues with implications for biomedical research and clinical practice.
苏木精和伊红(H&E)是用于医学诊断的金标准组织学染色剂,已经使用了一个多世纪。在此,我们研究了这种染色剂的近红外 II(NIR-II)荧光。我们观察到 H&E 染色剂中的苏木精成分有显著的近红外 II 发射。我们发现,使用常见的三价铝苏木精媒染剂,其发射强度可以通过内源性三价铁的可用性进行调节,并且在更高的氧化应激下,这种发射强度会增加。我们的机制研究发现,苏木精的发射报告了铁通过蛋白铁蛋白的核转位。在人肿瘤组织样本中,氧化应激生物标志物与苏木精 NIR-II 发射强度相关。在受疾病进展影响的人阿尔茨海默病脑组织区域中也观察到了染色剂的发射响应,这表明铁蛋白的核转位作为氧化应激反应在这些区域中得到了保留。这些发现表明,H&E 染色剂的 NIR-II 发射提供了组织中氧化还原信息的新来源,这对生物医学研究和临床实践具有重要意义。