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Highly specific characterization and discrimination of monosodium urate crystals in gouty arthritis based on aggregation-induced emission luminogens

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Abstract

Existing technologies used to detect monosodium urate (MSU) crystals for gout diagnosis are not ideal due to their low sensitivity and complexity of operation. The purpose of this study was to explore whether aggregation-induced emission luminogens (AIEgens) can be used for highly specific imaging of MSU crystals to assist in the diagnosis of gout. First, we developed a series of luminogens (i.e., tetraphenyl ethylene (TPE)-NH2, TPE-2NH2, TPE-4NH2, TPE-COOH, TPE-2COOH, TPE-4COOH, and TPE-Ketoalkyne), each of which was then evenly mixed with MSU crystals. Next, optimal fluorescence imaging of each of the luminogens was characterized by a confocal laser scanning microscope (CLSM). This approach was used for imaging standard samples of MSU, hydroxyapatite (HAP) crystals, and mixed samples with 1:1 mass ratio of MSU/HAP. We also imaged samples from mouse models of acute gouty arthritis, HAP deposition disease, and comorbidities of interest. Subsequently, CLSM imaging results were compared with those of compensated polarized light microscopy, and we assessed the biosafety of TPE-Ketoalkyne in the RAW264.7 cell line. Finally, CLSM time series and three-dimensional imaging were performed on MSU crystal samples from human gouty synovial fluid and tophi. As a promising candidate for MSU crystal labeling, TPE-Ketoalkyne was found to detect MSU crystals accurately and rapidly in standard samples, animal samples, and human samples, and could precisely distinguish gout from HAP deposition disease. This work demonstrates that TPE-Ketoalkyne is suitable for highly specific and timely imaging of MSU crystals in gouty arthritis and may facilitate future research on MSU crystal-related diseases.

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Acknowledgements

This work was supported by the Shanghai Science and Technology Committee (No. 22dz1204700), the National Key R&D Program of China (Nos. 2020YFA0803800 and 2017YFE0132200), the National Natural Science Foundation of China (Nos. 82072510, 21907034, 21788102, 21525417, and 51620105009), the Natural Science Foundation of Guangdong Province (Nos. 2019B030301003 and 2016A030312002) and the Innovation and Technology Commission of Hong Kong (No. ITC-CNERC14S01).

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  1. Wenjuan Wang, Guiquan Zhang, and Ziyi Chen contributed equally to this work.

Authors and Affiliations

  1. Department of Sports Medicine, Huashan Hospital, Fudan University, Shanghai, 200040, China

    Wenjuan Wang, Ziyi Chen, Hanlin Xu & Yinghui Hua

  2. State Key Laboratory of Luminescent Materials and Devices, Guangdong Provincial Key Laboratory of Luminescence from Molecular Aggregates, South China University of Technology, Guangzhou, 510640, China

    Guiquan Zhang, Rong Hu & Anjun Qin

  3. Center for Aggregation-Induced Emission, AlE Institute, South China University of Technology, Guangzhou, 510640, China

    Guiquan Zhang, Rong Hu & Anjun Qin

  4. School of Chemistry and Chemical Engineering, University of South China, Hengyang, 421001, China

    Rong Hu

  5. State Key Laboratory of Surface Physics, Department of Physics, Fudan University, Shanghai, 200433, China

    Bohan Zhang

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  1. Wenjuan Wang
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Contributions

WJW and RH designed the study. WJW, GQZ, ZYC, and BHZ participated in all the experiments. WJW, GQZ, and HLX performed the data analyses. WJW and GQZ wrote and revised the manuscript. RH, AJQ, and YHH supervised the entire study process.

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Correspondence to Rong Hu, Anjun Qin or Yinghui Hua.

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Ethical approval

All experiments involving mice were approved by the Animal Welfare and Ethics Group of the Department of Experimental Animal Science, Shanghai Medical College of Fudan University (Shanghai, China; Ethics Approval No. 2019020405). All experiments involving human specimen collection were approved by the Ethics Committee of Huashan Hospital (Shanghai, China; Ethics Approval No. KY2020-060).

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Wang, W., Zhang, G., Chen, Z. et al. Highly specific characterization and discrimination of monosodium urate crystals in gouty arthritis based on aggregation-induced emission luminogens. Bio-des. Manuf. 6, 704–717 (2023). https://doi.org/10.1007/s42242-023-00252-4

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