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Lanthanide Metal–Organic Framework Flowers for Proteome Profiling and Biomarker Identification in Ultratrace Biofluid Samples
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    Lanthanide Metal–Organic Framework Flowers for Proteome Profiling and Biomarker Identification in Ultratrace Biofluid Samples
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    • Shuang Zhang
      Shuang Zhang
      Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, People’s Republic of China
      State Key Laboratory of Oncogenes and Related Genes, Institute for Personalized Medicine, Shanghai Jiao Tong University, Shanghai 200030, People’s Republic of China
      More by Shuang Zhang
    • Zhixiao Xu
      Zhixiao Xu
      Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, People’s Republic of China
      State Key Laboratory of Oncogenes and Related Genes, Institute for Personalized Medicine, Shanghai Jiao Tong University, Shanghai 200030, People’s Republic of China
      More by Zhixiao Xu
    • Youming Chen
      Youming Chen
      Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, People’s Republic of China
      State Key Laboratory of Oncogenes and Related Genes, Institute for Personalized Medicine, Shanghai Jiao Tong University, Shanghai 200030, People’s Republic of China
      More by Youming Chen
    • Lai Jiang
      Lai Jiang
      Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, People’s Republic of China
      State Key Laboratory of Oncogenes and Related Genes, Institute for Personalized Medicine, Shanghai Jiao Tong University, Shanghai 200030, People’s Republic of China
      More by Lai Jiang
    • Aiting Wang
      Aiting Wang
      Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, People’s Republic of China
      State Key Laboratory of Oncogenes and Related Genes, Institute for Personalized Medicine, Shanghai Jiao Tong University, Shanghai 200030, People’s Republic of China
      More by Aiting Wang
    • Guangxia Shen
      Guangxia Shen
      Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, People’s Republic of China
      State Key Laboratory of Oncogenes and Related Genes, Institute for Personalized Medicine, Shanghai Jiao Tong University, Shanghai 200030, People’s Republic of China
    • Xianting Ding*
      Xianting Ding
      Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, People’s Republic of China
      State Key Laboratory of Oncogenes and Related Genes, Institute for Personalized Medicine, Shanghai Jiao Tong University, Shanghai 200030, People’s Republic of China
      *Email: [email protected]
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    ACS Nano

    Cite this: ACS Nano 2025, 19, 4, 4377–4390
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    https://doi.org/10.1021/acsnano.4c12280
    Published January 22, 2025
    Copyright © 2025 American Chemical Society

    Abstract

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    Identifying effective biomarkers has long been a persistent need for early diagnosis and targeted therapy of disease. While mass spectrometry-based label-free proteomics with trace cell has been demonstrated, deep proteomics with ultratrace human biofluid remains challenging due to low protein concentration, extremely limited patient sample volume, and substantial protein contact losses during preprocessing. Herein, we proposed and validated lanthanide metal–organic framework flowers (MOF-flowers), as effective materials, to trap and enrich protein in biofluid jointly through cation−π interaction and O–Ln coordination. We further developed a MOF-flower assisted simplified and single-pot Sample Preparation (Mass-SP) workflow that incorporates protein capture, digest, and peptide elute into one single PCR tube to maximally avoid adsorptive sample loss. We adopted Mass-SP to decipher aqueous humor (AH) proteome signatures from cataract and retinal vein occlusion (RVO) patients and quantified ∼3900 proteins in merely 1 μL of AH. Combined with machine learning, we further identified PFKL as a prioritization biomarker for RVO disease with the areas under the curves of 0.95 ± 0.04. Mass-SP presents a strategy to identify de novo biomarkers and explore potential therapeutic targets with extremely limited clinical human body fluid resources.

    Copyright © 2025 American Chemical Society

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    Supporting Information

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    The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsnano.4c12280.

    • TEM images and XPS spectrum of MOF-flowers; the assessment of protein absorption rates and proteomic performance of MOF-flowers at varying incubation times; the number of identified peptides within 30, 60, and 90 min gradient length; the number of identified peptides prepared by Mass-SP and SP3 kit within 90 min gradient length; GO analysis of all quantified proteins in AH samples; the PCA diagrams of cataract and RVO groups; performance comparison of different machine learning models in accuracy, precision, recall, F1 score, and specificity; and the LIME explanation (PDF)

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    This article is cited by 1 publications.

    1. Emily A. Reasoner, Hsin-Ju Chan, Timothy J. Aballo, Kylie J. Plouff, Seungwoo Noh, Ying Ge, Song Jin. In Situ Metal–Organic Framework Growth in Serum Encapsulates and Depletes Abundant Proteins for Integrated Plasma Proteomics. ACS Nano 2025, 19 (14) , 13968-13981. https://doi.org/10.1021/acsnano.4c18028

    ACS Nano

    Cite this: ACS Nano 2025, 19, 4, 4377–4390
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acsnano.4c12280
    Published January 22, 2025
    Copyright © 2025 American Chemical Society

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