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

作　　者：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 

机构地区：[1]CAS Key Laboratory of Interfacial Physics and Technology,Shanghai Institute of Applied Physics,Chinese Academy of Sciences,Shanghai 201800,China [2]Institute of Materiobiology,College of Sciences,Shanghai University,Shanghai 200444,China [3]Xiangfu Laboratory,Jiaxing 314102,China [4]State Key Laboratory of Coordination Chemistry,School of Chemistry and Chemical Engineering,Nanjing University,Nanjing 210023,China [5]Shanghai Synchrotron Radiation Facility,Shanghai Advanced Research Institute,Chinese Academy of Sciences,Shanghai 201210,China [6]National Synchrotron Radiation Laboratory,University of Science and Technology of China,Hefei 230026,China [7]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 [8]Zhangjiang Laboratory,Shanghai 201210,China [9]University of Chinese Academy of Sciences,Beijing 100049,China

出　　处：《National Science Review》2024年第11期154-165,共12页国家科学评论（英文版）

基　　金：supported by the National Key R&D Program of China(2023YFC3404200 to Y.Z.);the National Natural Science Foundation of China(T2188102 and 21991134 to C.F.,22325406 to J.L.,and 12305400 to Q.Y.);the New Cornerstone Investi-gator Program(to C.F.),the 2022 Shanghai‘Science and Tech-nology Innovation Action Plan’Fundamental Research Project(22JC1401203 to Y.Z.);the Xiangfu Lab Research Project(XF012022E0100 to C.F.).

摘　　要：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,Znluorly,for imaging endogenous zinc ions.Znluor ly 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 Aβaggregates and learning/memory impairments.Our study provides a generalizable strategy for organelle-specific theranostic applications.

关 键 词：DNA framework(DNF) TETRAHEDRON LYSOSOME zinc ions Alzheimer’s disease 

分 类 号：TM912[电气工程—电力电子与电力传动]