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Receptor-Mediated Cellular Uptake of Folate-Conjugated Fluorescent Nanodiamonds: A Combined Ensemble and Single-Particle Study

Authors

  • Bailin Zhang,

    1. Institute of Atomic and Molecular Sciences, Academia Sinica Taipei 106 (Taiwan)
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  • Yingqi Li,

    1. Institute of Atomic and Molecular Sciences, Academia Sinica Taipei 106 (Taiwan)
    2. Department of Chemistry College of Chemistry and Chemical Engineering, Shanxi University Taiyuan 030006 (P. R. China)
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  • Chia-Yi Fang,

    1. Institute of Atomic and Molecular Sciences, Academia Sinica Taipei 106 (Taiwan)
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  • Cheng-Chun Chang,

    1. Institute of Atomic and Molecular Sciences, Academia Sinica Taipei 106 (Taiwan)
    2. Department of Chemistry, National Taiwan Normal University Taipei 106 (Taiwan)
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  • Chao-Sheng Chen,

    1. Institute of Atomic and Molecular Sciences, Academia Sinica Taipei 106 (Taiwan)
    2. Department of Chemistry, National Taiwan Normal University Taipei 106 (Taiwan)
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  • Yi-Ying Chen,

    1. Institute of Atomic and Molecular Sciences, Academia Sinica Taipei 106 (Taiwan)
    2. Department of Chemistry, National Taiwan Normal University Taipei 106 (Taiwan)
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  • Huan-Cheng Chang

    Corresponding author
    1. Institute of Atomic and Molecular Sciences, Academia Sinica Taipei 106 (Taiwan)
    2. Department of Chemistry, National Taiwan Normal University Taipei 106 (Taiwan)
    • Institute of Atomic and Molecular Sciences, Academia Sinica Taipei 106 (Taiwan).
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Abstract

Fluorescent nanodiamonds (FNDs) are nontoxic and photostable nanomaterials, ideal for long-term in vivo imaging applications. This paper reports that FNDs with a size of ≈140 nm can be covalently conjugated with folic acid (FA) for receptor-mediated targeting of cancer cells at the single-particle level. The conjugation is made by using biocompatible polymers, such as polyethylene glycol, as crosslinked buffer layers. Ensemble-averaged measurements with flow cytometry indicate that more than 50% of the FA-conjugated FND particles can be internalized by the cells (such as HeLa cells) through receptor-mediated endocytosis, as confirmed by competitive inhibition assays. Confocal fluorescence microscopy reveals that these FND particles accumulate in the perinuclear region. The absolute number of FNDs internalized by HeLa cells after 3 h of incubation at a particle concentration of 10 µg mL−1 is in the range of 100 particles per cell. The receptor-mediated uptake process is further elucidated by single-particle tracking of 35-nm FNDs in three dimensions and real time during the endocytosis.

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