Recent Endeavors on Molecular Imaging for Mapping Metals in Biology
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Biophysics Reports
REVIEW
Recent Endeavors on Molecular Imaging for Mapping Metals in Biology Jing Gao1, Yuncong Chen1,2&, Zijian Guo1,2, Weijiang He1& 1
State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China
2
Chemistry and Biomedicine Innovation Center, Nanjing University, Nanjing 210023, China
Received: 2 June 2020 / Accepted: 2 August 2020 / Published online: 4 October 2020
Abstract
Transition metals such as zinc, copper and iron play vital roles in maintaining physiological functions and homeostasis of living systems. Molecular imaging, including two-photon imaging (TPI), bioluminescence imaging (BLI) and photoacoustic imaging (PAI), could act as non-invasive toolkits for capturing dynamic events in living cells, tissues and whole animals. Herein, we review the recent progress in the development of molecular probes for essential transition metals and their biological applications. We emphasize the contributions of metallostasis to health and disease, and discuss the future research directions about how to harness the great potential of metal sensors.
Graphic Abstract
Keywords Molecular imaging, Zinc, Copper, Iron
INTRODUCTION Iron, zinc and copper, the top three abundant transition metals in the human body, were well recognized for their essential roles in maintaining homeostasis and sustaining life. There were numerous examples of clinical diseases that were closely associated with metal
& Correspondence: [email protected] (Y. Chen), [email protected] (W. He)
Ó The Author(s) 2020
misregulation, such as Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS) and Parkinson’s disease (PD) (Bleackley and MacGillivray 2011). In this regard, careful maintenance of transition metal homeostasis is required in most living systems. Labile metal ions, part of the total metal pools, are weakly bound to ligands and can rapidly dissociate (Aron et al. 2015). Redox-active labile metals, such as copper and iron, can be harnessed to create new diagnostics and therapeutics (Chang 2015). Ferrous iron
159 | October 2020 | Volume 6 | Issue 5
REVIEW
J. Gao et al.
(Fe2?) is oxidized into ferric iron (Fe3?) through reaction with hydrogen peroxide (H2O2), leading to the formation of highly reactive hydroxyl radicals (OH), referred to as the Fenton reaction. Fe3? is reduced back to Fe2? via reaction with superoxide radicals (O2.–). This redox cycle is called Harber–Weiss reaction (Hassannia et al. 2019). Like iron, copper (Cu? and Cu2?) can transform between two oxidation states under biological conditions. These metals can also undergo kinetically appreciable ligand exchange with sensors that respond to metal binding or reaction with an alteration in signal (light or sound) output (Ackerman et al. 2017). Fluorescence imaging (FLI) has been widely used in identifying diversified living processes. Providing a potentially non-invasive set of tools with spatial and temporal resolution, molecular imaging drives scientists to peer into
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