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De Novo-Designed Near-Infrared Nanoaggregates for Super-Resolution Monitoring of Lysosomes in Cells, in Whole Organoids, and in Vivo

  • Hongbao Fang
    Hongbao Fang
    State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, Jiangsu 210023, P. R. China
    Department of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, United States
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  • , 
  • Shankun Yao
    Shankun Yao
    State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, Jiangsu 210023, P. R. China
    More by Shankun Yao
  • , 
  • Qixin Chen
    Qixin Chen
    Department of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, United States
    More by Qixin Chen
  • , 
  • Chunyan Liu
    Chunyan Liu
    Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio 45229, United States
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  • , 
  • Yuqi Cai
    Yuqi Cai
    Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio 45229, United States
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  • , 
  • Shanshan Geng
    Shanshan Geng
    State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, Jiangsu 210023, P. R. China
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  • , 
  • Yang Bai
    Yang Bai
    State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, Jiangsu 210023, P. R. China
    More by Yang Bai
  • , 
  • Zhiqi Tian
    Zhiqi Tian
    Department of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, United States
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  • , 
  • Amanda L. Zacharias
    Amanda L. Zacharias
    Division of Developmental Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio 45229, United States
    Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, United States
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  • , 
  • Takanori Takebe
    Takanori Takebe
    Division of Gastroenterology, Hepatology and Nutrition,  Center for Stem Cell and Organoid Medicine (CuSTOM),  Division of Developmental Biology  and  Division of Endocrinology, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio 45229, United States
    Institute of Research, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan
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  • , 
  • Yuncong Chen*
    Yuncong Chen
    State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, Jiangsu 210023, P. R. China
    *(Y.C.) E-mail: [email protected]
    More by Yuncong Chen
    Orcidhttp://orcid.org/0000-0002-8406-4866
  • , 
  • Zijian Guo
    Zijian Guo
    State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, Jiangsu 210023, P. R. China
    More by Zijian Guo
    Orcidhttp://orcid.org/0000-0003-4986-9308
  • , 
  • Weijiang He*
    Weijiang He
    State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, Jiangsu 210023, P. R. China
    *(W.H.) E-mail: [email protected]
    More by Weijiang He
    Orcidhttp://orcid.org/0000-0002-3157-5769
  • , and 
  • Jiajie Diao*
    Jiajie Diao
    Department of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, United States
    *(J.D.) E-mail: [email protected]
    More by Jiajie Diao
    Orcidhttp://orcid.org/0000-0003-4288-3203
Cite this: ACS Nano 2019, 13, 12, 14426–14436
Publication Date (Web):December 4, 2019
https://doi.org/10.1021/acsnano.9b08011
Copyright © 2019 American Chemical Society
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    Abstract

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    As the cleaners of cells, lysosomes play an important role in circulating organic matter within cells, recovering damaged organelles, and removing waste via endocytosis. Because lysosome dysfunction is associated with various diseases—lysosomal storage diseases, inherited diseases, rheumatoid arthritis, and even shock—it is vital to monitor the movement of lysosomes in cells and in vivo. To that purpose, a method of optical imaging, super-resolution imaging technology (e.g., SIM and STORM), can overcome the limitations of traditional optical imaging and afford a range of possibilities for fluorescence imaging. However, the short wavelength excitation and easy photobleaching of super-resolution fluorescence probes somewhat problematize super-resolution imaging. As described herein, we designed a low-toxicity, photostable, near-infrared small molecule fluorescence probe HD-Br for use in the super-resolution imaging of lysosomes. The interaction of lysosomes and mitochondria was dynamically traced while using the probe’s properties to label the lysosomes. Because the probe has the optimal near-infrared excitation and emission wavelengths, liver organoid 3D imaging and Caenorhabditis elegans imaging were also performed. Altogether, our findings indicate valuable approaches and techniques for super-resolution 3D and in vivo imaging.

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