biostudies-literatureGao YNew Cornerstone Investigator ProgramXiangfu Lab Research ProjectFundamental Research ProjectNational Natural Science Foundation of ChinaScience and Technology Innovation Action PlanNational Key Research and Development Program of Chinanwae307https://www.ebi.ac.uk/biostudies/studies/S-EPMC11493095biostudies-literatureUnknown11(11)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, Znluor_ly, 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-targNational science reviewTargeted imaging of lysosomal zinc ions with a tetrahedral DNA framework fluorescent reporter.PMC1149309522325406T218810212305400XF012022E010022JC1401203219911342023YFC3404200Geng SLi JYan QGuo ZZhang JZhu YLi QWang LLiu XLi WGuan YJia SHe WGao YChen YFan CZhu SfalseTargeted imaging of lysosomal zinc ions with a tetrahedral DNA framework fluorescent reporter.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, Znluor_ly, 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-targ2024-01-01T00:00:00Z2024 Nov2025-04-27T02:10:13.186Z2025-04-06T18:29:07.088ZS-EPMC114930953944026010.1093/nsr/nwae307