Zhu Jianping, Graziotto Marcus E, Cottam Veronica, Hawtrey Tom, Adair Liam D, Trist Benjamin G, Pham Nguyen T H, Rouaen Jourdin R C, Ohno Carolyn, Heisler Marcus, Vittorio Orazio, Double Kay L, New Elizabeth J
School of Chemistry, The University of Sydney, Sydney, NSW 2006, Australia.
Brain and Mind Centre and School of Medical Sciences (Neuroscience), The University of Sydney, Sydney, NSW 2006, Australia.
ACS Sens. 2024 Jun 28;9(6):2858-2868. doi: 10.1021/acssensors.3c02549. Epub 2024 May 24.
Copper participates in a range of critical functions in the nervous system and human brain. Disturbances in brain copper content is strongly associated with neurological diseases. For example, changes in the level and distribution of copper are reported in neuroblastoma, Alzheimer's disease, and Lewy body disorders, such as Parkinson disease and dementia with Lewy bodies (DLB). There is a need for more sensitive techniques to measure intracellular copper levels to have a better understanding of the role of copper homeostasis in neuronal disorders. Here, we report a reaction-based near-infrared (NIR) ratiometric fluorescent probe for imaging Cu in biological samples. High stability and selectivity of enabled the probe to be deployed as a sensor in a range of systems, including SH-SY5Y cells and neuroblastoma tumors. Furthermore, it can be used in plant cells, reporting on copper added to roots. We also used to explore Cu levels and distribution in post-mortem brain tissues from patients with DLB. We found significant decreases in Cu content in the cytoplasm, neurons, and extraneuronal space in the degenerating substantia nigra in DLB compared with healthy age-matched control tissues. These findings enhance our understanding of Cu dysregulation in Lewy body disorders. Our probe also shows promise as a photoacoustic imaging agent, with potential for applications in bimodal imaging.
铜在神经系统和人类大脑中参与一系列关键功能。脑铜含量的紊乱与神经疾病密切相关。例如，据报道在神经母细胞瘤、阿尔茨海默病以及路易体疾病（如帕金森病和路易体痴呆症）中，铜的水平和分布会发生变化。需要更灵敏的技术来测量细胞内铜水平，以便更好地理解铜稳态在神经元疾病中的作用。在此，我们报告一种基于反应的近红外（NIR）比率荧光探针，用于对生物样品中的铜进行成像。该探针的高稳定性和选择性使其能够作为传感器应用于一系列系统，包括SH-SY5Y细胞和神经母细胞瘤肿瘤。此外，它可用于植物细胞，检测添加到根部的铜。我们还使用该探针探索路易体痴呆症患者死后脑组织中的铜水平和分布。我们发现，与年龄匹配的健康对照组织相比，路易体痴呆症患者黑质退变区域的细胞质、神经元和神经外间隙中的铜含量显著降低。这些发现加深了我们对路易体疾病中铜失调的理解。我们的探针还显示出作为光声成像剂的潜力，具有在双模态成像中应用的可能性。
