Targeted 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<sub>ly</sub>, for imaging endogenous zinc ions. Znluor<sub>ly</sub> 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 Znluor<sub>ly</sub>, 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.
Authors
- Shanshan Geng (ORCID: https://orcid.org/0000-0003-0097-6284)
- Chunhai Fan (ORCID: https://orcid.org/0000-0002-7171-7338)
- Ying Jie Zhu (ORCID: https://orcid.org/0000-0003-0418-919X)
- Weijiang He (ORCID: https://orcid.org/0000-0002-3157-5769)
- Yuncong Chen (ORCID: https://orcid.org/0000-0002-8406-4866)
- Zijian Guo (ORCID: https://orcid.org/0000-0003-4986-9308)
- Qinglong Yan (ORCID: https://orcid.org/0000-0002-3928-5176)
- Sisi Jia (ORCID: https://orcid.org/0000-0002-5877-5138)
- Jichao Zhang (ORCID: https://orcid.org/0000-0002-7400-6726)
- Wei Li (ORCID: https://orcid.org/0000-0002-5277-6850)
- Shitai Zhu
- Qian Li (ORCID: https://orcid.org/0000-0002-1166-6583)
- Xia Liu (ORCID: https://orcid.org/0000-0002-0039-4754)
- Lihua Wang (ORCID: https://orcid.org/0000-0002-6198-7561)
- Jiang Li (ORCID: https://orcid.org/0000-0003-2372-6624)
- Yong Guan (ORCID: https://orcid.org/0000-0003-0445-1848)
- Yue Gao (ORCID: https://orcid.org/0000-0003-2038-0146)
Institutions
- Shanghai University (CN)
- University of Science and Technology of China (CN)
- Shanghai Jiao Tong University (CN)
- Shanghai Advanced Research Institute (CN)
- Shanghai Zhangjiang Laboratory (CN)
- Shanghai Institute of Applied Physics (CN)
- National Synchrotron Radiation Laboratory (CN)
- University of Chinese Academy of Sciences (CN)
- Nanjing University (CN)
Publication Details
- Journal
- National Science Review
- Published
- 2024-09-12
- DOI
- https://doi.org/10.1093/nsr/nwae307
- Citations
- 8
- Primary Topic
- Advanced biosensing and bioanalysis techniques
- Type
- article
- Field-Weighted Citation Impact
- 1.87
Funders
- Salt Science Research Foundation
- National Natural Science Foundation of China
- National Synchrotron Radiation Laboratory
- National Key Research and Development Program of China