首页|Targeted imaging of lysosomal zinc ions with a tetrahedral DNA framework fluorescent reporter

Targeted imaging of lysosomal zinc ions with a tetrahedral DNA framework fluorescent reporter

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Abnormal levels of zinc ions within endo-lysosomes have been implicated in the progression of Alzheimer's disease(AD),yet the detection of low-concentration zinc ions at the organelle level remains challenging.Here we report the design of an endo-lysosome-targeted fluorescent reporter,Znluoriy,for imaging endogenous zinc ions.Znluoriy is constructed from an amphiphilic DNA framework(DNF)with programmable size and shape,which can encapsulate zinc-responsive fluorophores within its hydrophobic nanocavity.We find that the tetrahedral DNFs of 20 bp in the edge length are effectively located within endo-lysosomes,which can detect zinc ions with a detection limit of～31.9 nM(a sensitivity that is～2.5 times that of the free fluorophore).Given the organelle-targeting ability and high zinc sensitivity of Znluorly,we employ it to detect endogenous endo-lysosomal zinc ions in neuron cells.We monitor the dynamics of zinc levels in AD model cells and zebrafish,corroborating the positive correlation between zinc levels and AD hallmarks including Aβ aggregates and learning/memory impairments.Our study provides a generalizable strategy for organelle-specific theranostic applications.

DNA framework(DNF)tetrahedronlysosomezinc ionsAlzheimer's disease

Yue Gao、Xia Liu、Wei Li、Yuncong Chen、Shitai Zhu、Qinglong Yan、Shanshan Geng、Jichao Zhang、Yong Guan、Qian Li、Sisi Jia、Lihua Wang、Jiang Li、Weijiang He、Chunhai Fan、Zijian Guo、Ying Zhu

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CAS Key Laboratory of Interfacial Physics and Technology,Shanghai Institute of Applied Physics,Chinese Academy of Sciences,Shanghai 201800,China

Institute of Materiobiology,College of Sciences,Shanghai University,Shanghai 200444,China

University of Chinese Academy of Sciences,Beijing 100049,China

Xiangfu Laboratory,Jiaxing 314102,China

State Key Laboratory of Coordination Chemistry,School of Chemistry and Chemical Engineering,Nanjing University,Nanjing 210023,China

Shanghai Synchrotron Radiation Facility,Shanghai Advanced Research Institute,Chinese Academy of Sciences,Shanghai 201210,China

National Synchrotron Radiation Laboratory,University of Science and Technology of China,Hefei 230026,China

School of Chemistry and Chemical Engineering,New Cornerstone Science Laboratory,Frontiers Science Center for Transformative Molecules and National Center for Translational Medicine,Shanghai Jiao Tong University,Shanghai 200240,China

Zhangjiang Laboratory,Shanghai 201210,China

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2024

10.1093/nsr/nwae307

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ISSN：
年,卷(期)：2024.11(11)