Cyclen-Based Cationic Lipids Containing Carbamate Linkages as Efficient Gene Delivery Vectors with Low Toxicity

Authors

  • Dr. Qing-Dong Huang,

    1. Key Laboratory of Green Chemistry and Technology (Ministry of Education), College of Chemistry, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610064 (P. R. China)
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    • These authors contributed equally to this work.

  • Jiang Ren,

    1. Key Laboratory of Green Chemistry and Technology (Ministry of Education), College of Chemistry, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610064 (P. R. China)
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    • These authors contributed equally to this work.

  • Hong Chen,

    1. Key Laboratory of Green Chemistry and Technology (Ministry of Education), College of Chemistry, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610064 (P. R. China)
    2. Department of Basic Science, Rongchang Campus, Southwest China University, Chongqing 402460 (P. R. China)
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  • Wen-Jing Ou,

    1. Key Laboratory of Green Chemistry and Technology (Ministry of Education), College of Chemistry, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610064 (P. R. China)
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  • Dr. Ji Zhang,

    Corresponding author
    1. Key Laboratory of Green Chemistry and Technology (Ministry of Education), College of Chemistry, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610064 (P. R. China)
    • Key Laboratory of Green Chemistry and Technology (Ministry of Education), College of Chemistry, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610064 (P. R. China)
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  • Yun Fu,

    1. Key Laboratory of Green Chemistry and Technology (Ministry of Education), College of Chemistry, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610064 (P. R. China)
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  • Prof. Dr. Wen Zhu,

    Corresponding author
    1. Key Laboratory of Green Chemistry and Technology (Ministry of Education), College of Chemistry, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610064 (P. R. China)
    • Key Laboratory of Green Chemistry and Technology (Ministry of Education), College of Chemistry, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610064 (P. R. China)
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  • Prof. Dr. Xiao-Qi Yu

    Corresponding author
    1. Key Laboratory of Green Chemistry and Technology (Ministry of Education), College of Chemistry, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610064 (P. R. China)
    • Key Laboratory of Green Chemistry and Technology (Ministry of Education), College of Chemistry, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610064 (P. R. China)
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Abstract

Two novel cationic lipids based on protonated cyclen and steroid (cholesterol or diosgenin) moieties with carbamate linkage have been designed and synthesized for gene delivery. Cationic liposomes were easily prepared from each of these lipids individually or from the mixtures of each cationic lipid and dioleoylphosphatidyl ethanolamine (DOPE). Several studies including dynamic light scattering, gel retardation assay, ethidium bromide intercalation assay, and transmission electron microscopy (TEM) imaging demonstrate that these amphiphilic molecules are able to bind and compact DNA into nanoparticles which may act as nonviral gene delivery agents. Results from in vitro transfection show that in association with (DOPE), two cationic lipids can induce effective gene transfection in HEK 293, A549, and H460 cells. Especially, in tumor cells (A549 and H460), the gene transfection efficiency of two cationic lipids were found to be higher than that of commercially available Lipofectamine 2000. The lipoplexes formed from both cationic lipids were found to have low cytotoxicity in three cell lines even at high N/P ratios.

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