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Targeted Cellular Uptake and siRNA Silencing by Quantum-Dot Nanoparticles Coated with β-Cyclodextrin Coupled to Amino Acids

Authors

  • Mei-Xia Zhao,

    1. MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275 (P. R. China), Fax: (+86) 20-8411-2245
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  • Jin-Ming Li,

    1. MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275 (P. R. China), Fax: (+86) 20-8411-2245
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  • Lingyan Du,

    1. State Key Laboratory of Natural and Biomimetic Drug, Department of Chemical Biology, School of Pharmaceutical Science, Peking University, Beijing 100191 (P. R. China), Fax: (+86) 10-8280-5611
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  • Dr. Cai-Ping Tan,

    1. MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275 (P. R. China), Fax: (+86) 20-8411-2245
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  • Dr. Qing Xia,

    Corresponding author
    1. State Key Laboratory of Natural and Biomimetic Drug, Department of Chemical Biology, School of Pharmaceutical Science, Peking University, Beijing 100191 (P. R. China), Fax: (+86) 10-8280-5611
    • State Key Laboratory of Natural and Biomimetic Drug, Department of Chemical Biology, School of Pharmaceutical Science, Peking University, Beijing 100191 (P. R. China), Fax: (+86) 10-8280-5611
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  • Prof. Zong-Wan Mao,

    Corresponding author
    1. MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275 (P. R. China), Fax: (+86) 20-8411-2245
    2. State Key Laboratory of Natural and Biomimetic Drug, Department of Chemical Biology, School of Pharmaceutical Science, Peking University, Beijing 100191 (P. R. China), Fax: (+86) 10-8280-5611
    • MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275 (P. R. China), Fax: (+86) 20-8411-2245
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  • Prof. Liang-Nian Ji

    1. MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275 (P. R. China), Fax: (+86) 20-8411-2245
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Abstract

Quantum dots (QDs) have the potential to serve as photostable beacons to track siRNA delivery, which is fast becoming an attractive approach to probe gene function in cells. In this paper, we synthesized QD nanoparticles coated with β-cyclodextrin (β-CD) coupled to amino acids with different surface charges (positive, negative, and neutral) through direct ligand-exchange reactions and used them to deliver siRNA. We found that these QDs are diffluent in biological buffer with high colloidal stability and have strong optical emission properties similar to those of tri-n-octylphosphine oxide (TOPO)-coated QDs and also have a long fluorescence lifetime (12.5 ns for L-His-β-CD-coated CdSe/ZnSe QDs). The results of in vitro cytotoxicity and internalization of these modified QDs in normal and cancer cells showed that the β-CD coupled to amino acid outlayers greatly improved the biocompatibility of QDs, and conferred with lower cytotoxicity even at very high concentration. In particular, the L-His-β-CD-coated CdSe/ZnSe QDs presented lower cytotoxicity to these cells (CC50 value is 180.6±3.4 μg mL−1 in ECV-304 cells for 48 h). Transmission electron microscope (TEM) images showed that the QDs were localized in vesicles in the cytoplasm of the cells. Furthermore, compared with existing transfection agents, gene-silencing efficiency of the modified QDs was slightly improved for HPV18 E6 gene in HeLa cells by gel electrophoresis analysis. Finally, the unique optical properties of QDs allow visible imaging of siRNA delivery in live cells. Taken together, our study not only provides new insights into the mechanisms of amino acid mediated delivery, but also greatly facilities the monitoring of gene-silencing studies.

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