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Receptor‐Mediated Cellular Uptake of Folate‐Conjugated Fluorescent Nanodiamonds: A Combined Ensemble and Single‐Particle Study
Author(s) -
Zhang Bailin,
Li Yingqi,
Fang ChiaYi,
Chang ChengChun,
Chen ChaoSheng,
Chen YiYing,
Chang HuanCheng
Publication year - 2009
Publication title -
small
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.785
H-Index - 236
eISSN - 1613-6829
pISSN - 1613-6810
DOI - 10.1002/smll.200900725
Subject(s) - endocytosis , hela , receptor mediated endocytosis , biophysics , flow cytometry , folate receptor , conjugated system , fluorescence microscope , materials science , confocal microscopy , fluorescence , cancer cell , nanotechnology , chemistry , receptor , cell , microbiology and biotechnology , polymer , biochemistry , biology , cancer , genetics , physics , quantum mechanics , composite material
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.