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Galactose Encapsulated Multifunctional Nanoparticle for HepG2 Cell Internalization

Authors

  • Chian-Hui Lai,

    1. Department of Chemistry, National Tsing Hua University, Hsin-chu (Taiwan) #101, Sec. 2, Kuang-Fu Road, Hsinchu, Taiwan 30013 (Taiwan)
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  • Chia-Yi Lin,

    1. Department of Life Science, National Tsing Hua University, Hsin-chu (Taiwan) #101, Sec. 2, Kuang-Fu Road, Hsinchu, Taiwan 30013 (Taiwan)
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  • Huan-Ting Wu,

    1. Department of Chemistry, National Tsing Hua University, Hsin-chu (Taiwan) #101, Sec. 2, Kuang-Fu Road, Hsinchu, Taiwan 30013 (Taiwan)
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  • Hau-Shien Chan,

    1. Department of Life Science, National Tsing Hua University, Hsin-chu (Taiwan) #101, Sec. 2, Kuang-Fu Road, Hsinchu, Taiwan 30013 (Taiwan)
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  • Yung-Jen Chuang,

    1. Department of Life Science, National Tsing Hua University, Hsin-chu (Taiwan) #101, Sec. 2, Kuang-Fu Road, Hsinchu, Taiwan 30013 (Taiwan)
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  • Chien-Tien Chen,

    1. Department of Chemistry, National Tsing Hua University, Hsin-chu (Taiwan) #101, Sec. 2, Kuang-Fu Road, Hsinchu, Taiwan 30013 (Taiwan)
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  • Chun-Cheng Lin

    Corresponding author
    1. Department of Chemistry, National Tsing Hua University, Hsin-chu (Taiwan) #101, Sec. 2, Kuang-Fu Road, Hsinchu, Taiwan 30013 (Taiwan)
    • Department of Chemistry National Tsing Hua University Hsin-chu (Taiwan) #101, Sec. 2, Kuang-Fu Road, Hsinchu, Taiwan 30013 (Taiwan)
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Abstract

The fluorescent dye Cy3 and galactose derivatives are covalently assembled with different ratios on the surfaces of magnetic nanoparticles (MNPs) to produce multifunctional HepG2 cancer cell–targeting agents and the effect of ligand spatial orientation on the MNP surface is investigated on targeting specificity. By using a mixture of bis-N-hydroxysuccinimide ester (a bifunctional linker) and OSu-activated Cy3 (w/w = 30:1), stable and quantifiable fluorescent MNPs (Cy3@MNPs) are synthesized that could be subsequently loaded with galactosyl ligands. A mono-antennary and two different tri-antennary galactosyl ligands are individually immobilized on Cy3@MNPs, and the uptake efficiencies of the resulting galactosyl Cy3@MNPs by HepG2 and HeLa cells are investigated using confocal microscopy. The confocal images show that galactosyl Cy3@MNPs are sprayed over cytoplasm of the HepG2 cells, indicating that the MNP uptake occurs via receptor-mediated endocytosis that is followed by release from endosomes. The results also reveal that the ligand spatial orientation affects the efficiency of the receptor-mediated endocytosis and one of the tri-antennary galactosyl ligands shows the best uptake efficiency owing to the optimal spatial presentation of the galactosyl moieties. Overall, it is shown that the MNP is a good ligand carrier and that, when pre-assembled, the multivalent ligand structure enhances the interactions between the surface ligands of the MNPs and receptors of HepG2 cells. Additionally, the galactosyl Cy3@MNPs are not cytotoxic, indicating that they may potentially be used for in vivo applications.

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