image: a, Structure and chemical principle of Znluorly. b, Application of Znluorly in imaging endogenous Zn2+ in neural cells of the AD model zebrafish. c, Principle of the endo-lysosome-targeting ability of Znluorly.
Credit: ©Science China Press
This study is led by Prof. Ying Zhu (Shanghai University), Prof. Zijian Guo (Nanjing University) and Prof. Chunhai Fan (Shanghai Jiao Tong University). They developed a shape-dependent framework nucleic acid probe for zinc ions, Znluorly, which is capable of efficiently targeting endosomes and lysosomes in live cells. By utilizing fluorescence imaging and synchrotron-based X-ray microscopy, they studied the dynamic changes of endogenous zinc ions.
The zinc ion probe is constructed based on an amphiphilic DNA framework structure with programmable size and shape, featuring a hydrophobic nano-cavity that encapsulates zinc ion-responsive fluorescent molecules. It was found that a tetrahedral framework nucleic acid with an edge length of 20 base pairs can effectively localize within the endo-lysosomes. Through dynamic monitoring of zinc levels in Alzheimer’s disease model cells and zebrafish, the researchers confirmed a positive correlation between zinc levels and Alzheimer's disease markers, including Aβ aggregation and learning/memory impairments.
Synchrotron-based X-ray microscopy further revealed that as Alzheimer's disease progresses, intracellular zinc levels, along with other disease-related metal elements, increase. This demonstrated the probe’s ability to monitor dynamic zinc ion changes in Alzheimer’s disease models.
This work was supported by the BL15U1 hard X-ray micro-focusing beamline of Shanghai Synchrotron Radiation Facility (SSRF, China) and BL07W soft X-ray microscopy beamline of National Synchrotron Radiation Laboratory (NSRL, China).
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See the article:
Targeted imaging of lysosomal zinc ions with a tetrahedral DNA framework fluorescent reporter
https://doi.org/10.1093/nsr/nwae307
Journal
National Science Review