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Anionic Liposomes Increase the Efficiency of Adenovirus-Mediated Gene Transfer to Coxsackie-Adenovirus Receptor Deficient Cells

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    Anionic Liposomes Increase the Efficiency of Adenovirus-Mediated Gene Transfer to Coxsackie-Adenovirus Receptor Deficient Cells
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    Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, P. R. China, and Luzhou Medical College, Luzhou, Sichuan, P. R. China
    * Corresponding author. Mailing address: Sichuan University, West China School of Pharmacy, No. 17 Block 3 Southern Renmin Road, Chengdu, Sichuan, 610041 China. Tel/fax: +86-28-85502307. E-mail: [email protected]
    †Sichuan University.
    ‡Luzhou Medical College.
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    Molecular Pharmaceutics

    Cite this: Mol. Pharmaceutics 2010, 7, 1, 105–115
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    https://doi.org/10.1021/mp900151k
    Published December 7, 2009
    Copyright © 2009 American Chemical Society
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    Abstract

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    Despite remarkable progress in the research of both viral and nonviral gene delivery vectors, the drawbacks in each delivery system have limited their clinical applications. Therefore, one of the concepts for developing novel vectors is to overcome the limitations of individual vectors by combining them. In the current study, adenoviral vectors were formulated with anionic liposomes to protect them from neutralizing antibodies and to improve their transduction efficiency in Coxsackievirus-adenovirus receptor (CAR) deficient cells. A calcium-induced phase change method was applied to encapsulate adenovirus 5 (Ad5) into anionic liposomes to formulate the complexes of Ad5 and anionic liposomes (Ad5−AL). Meanwhile, the complexes of Ad5 and cationic liposomes (Ad5−CL) were also prepared as controls. LacZ gene expression in CAR overexpressing cells (A549) and CAR deficient cells (CHO and MDCK) was measured by either qualitative or quantitative detection. Confocal laser scanning microscopy was performed to determine intracellular location of Ad5 after their infection. Human sera with a high titer of antiadenovirus antibody were used to assess the neutralizing antibody protection ability of the complexed vectors. Accompanying the enhanced gene expression, a high ability to introduce Ad5 into cytoplasm and nucleus mediated by Ad5−AL was also observed in CAR deficient cells. Additionally, antibody neutralizing assay indicated that neutralizing serum inhibited naked Ad5 and Ad5−CL at rather higher dilution than Ad5−AL, which demonstrated Ad5−AL was more capable of protecting Ad5 from neutralizing than Ad5−CL. In conclusion, anionic liposomes prepared by the calcium-induced phase change method could significantly enhance the transduction ability of Ad5 in CAR deficient cells.

    Copyright © 2009 American Chemical Society

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    Supporting Information

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    Transfection efficiency comparison of naked Ad5, Ad5−AL and Ad5−CL, in which the Ad5−CL and the naked Ad5 formulations were prepared exactly the same way the Ad5−AL were prepared. This material is available free of charge via the Internet at http://pubs.acs.org.

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    Molecular Pharmaceutics

    Cite this: Mol. Pharmaceutics 2010, 7, 1, 105–115
    Click to copy citationCitation copied!
    https://doi.org/10.1021/mp900151k
    Published December 7, 2009
    Copyright © 2009 American Chemical Society
    Request reuse permissions

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