Near-Infrared Ratiometric Fluorescent Probe for Detecting Endogenous Cu2+ in the Brain

被引：22

作者：

Zhu, Jianping ^{[1
]}

Graziotto, Marcus E. ^{[1
]}

Cottam, Veronica ^{[2
,3
]}

Hawtrey, Tom ^{[1
,4
,5
]}

Adair, Liam D. ^{[1
,4
,5
]}

Trist, Benjamin G. ^{[2
,3
]}

Pham, Nguyen T. H. ^{[6
]}

Rouaen, Jourdin R. C. ^{[7
]}

Ohno, Carolyn ^{[8
]}

Heisler, Marcus ^{[8
]}

Vittorio, Orazio ^{[7
,9
]}

Double, Kay L. ^{[2
,3
]}

New, Elizabeth J. ^{[1
,4
,5
]}

机构：

[1] Univ Sydney, Sch Chem, Sydney, NSW 2006, Australia

[2] Univ Sydney, Brain & Mind Ctr, Sydney, NSW 2006, Australia

[3] Univ Sydney, Sch Med Sci Neurosci, Sydney, NSW 2006, Australia

[4] Univ Sydney, Sydney Nano Inst, Sydney, NSW 2006, Australia

[5] Univ Sydney, Australian Res Council, Ctr Excellence Innovat Peptide & Prot Sci, Sydney, NSW 2006, Australia

[6] Univ Sydney, Sydney Imaging, Core Res Facil, Sydney, NSW 2006, Australia

[7] Univ New South Wales Sydney, Lowy Canc Res Ctr, Childrens Canc Inst, Randwick, NSW 2052, Australia

[8] Univ Sydney, Sch Life & Environm Sci, Sydney, NSW 2006, Australia

[9] Univ New South Wales, Sch Biomed Sci, Kensington, NSW 2031, Australia

来源：

ACS SENSORS | 2024年 / 9卷 / 06期

基金：

澳大利亚研究理事会; 英国医学研究理事会;

关键词：

copper; fluorescent probe; activity-based sensing; photoacoustic imaging; cyanine; neuroblastoma; Lewy body disease; Arabidopsis; SOFT ACIDS; TURN-ON; COPPER; IRON; DEMENTIA; REGIONS; CELLS; HARD; ZINC; VIVO;

D O I：

10.1021/acssensors.3c02549

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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 CyCu1 for imaging Cu2+ in biological samples. High stability and selectivity of CyCu1 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 Arabidopsis roots. We also used CyCu1 to explore Cu2+ levels and distribution in post-mortem brain tissues from patients with DLB. We found significant decreases in Cu2+ 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 Cu2+ dysregulation in Lewy body disorders. Our probe also shows promise as a photoacoustic imaging agent, with potential for applications in bimodal imaging.

引用

页码：2858 / 2868

页数：11

共 65 条

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