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Surface-Mediated Nucleic Acid Delivery by Lipoplexes Prepared in Microwell Arrays

Authors

  • Yun Wu,

    1. Nanoscale Science and Engineering Center for Affordable, Nanoengineering, The Ohio State University, 174 W 18th Avenue, Room 1012, Columbus, Ohio 43210, USA, Tel: +1 614 292 2408;, Fax:+1 614 292 8685
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  • Megan Cavanaugh Terp,

    1. Nanoscale Science and Engineering Center for Affordable, Nanoengineering, The Ohio State University, 174 W 18th Avenue, Room 1012, Columbus, Ohio 43210, USA, Tel: +1 614 292 2408;, Fax:+1 614 292 8685
    2. Department of Chemical and Bimolecular Engineering, The Ohio State University, 140 W 19th Avenue, Room 125A, Columbus, Ohio 43210, USA
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  • Kwang Joo Kwak,

    1. Nanoscale Science and Engineering Center for Affordable, Nanoengineering, The Ohio State University, 174 W 18th Avenue, Room 1012, Columbus, Ohio 43210, USA, Tel: +1 614 292 2408;, Fax:+1 614 292 8685
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  • Daniel Gallego-Perez,

    1. Nanoscale Science and Engineering Center for Affordable, Nanoengineering, The Ohio State University, 174 W 18th Avenue, Room 1012, Columbus, Ohio 43210, USA, Tel: +1 614 292 2408;, Fax:+1 614 292 8685
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  • Serge P. Nana-Sinkam,

    1. Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, DHLRI, 473 W 12th Avenue, Room 201, Columbus, Ohio 43210, USA
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  • L. James Lee

    Corresponding author
    1. Nanoscale Science and Engineering Center for Affordable, Nanoengineering, The Ohio State University, 174 W 18th Avenue, Room 1012, Columbus, Ohio 43210, USA, Tel: +1 614 292 2408;, Fax:+1 614 292 8685
    • Nanoscale Science and Engineering Center for Affordable, Nanoengineering of Polymeric Biomedical Devices, The Ohio State University, 174 W 18th Avenue, Room 1012, Columbus, Ohio 43210, USA, Tel: +1 614 292 2408;, Fax:+1 614 292 8685.

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Abstract

Many delivery methods have been developed to improve the therapeutic efficacy and facilitate the clinical translation of nucleic acid-based therapeutics. A facile surface-mediated nucleic acid delivery by lipoplexes is prepared in a microwell array, which combines the advantages of lipoplexes as an efficient carrier system, surface-mediated delivery, and the control of surface topography. Uniform disc-like lipoplexes containing nucleic acids are formed in the microwell array with a diameter of ∼818 nm and thickness of ∼195 nm. The microwell array-mediated delivery of lipoplexes containing FAM-oligodeoxynucleotides is ∼18.6 and ∼10.6 times more efficient than the conventional transfection method in an adherent cell line (A549 non-small cell lung cancer cells) and a suspension cell line (KG-1a acute myelogenous leukemia cells), respectively. MicroRNA-29b is then used as a model nucleic acid to investigate the therapeutic efficacy of lipoplexes delivered by the microwell array. Compared to conventional transfection methods, the effective therapeutic dosage of microRNA-29b is reduced from the microgram level to the nanogram level by lipoplexes prepared in the microwell array. The microwell array is also a very flexible platform. Both nucleic acid therapeutics and imaging reagents are incorporated in lipoplexes and successfully delivered to A549 cells, demonstrating its potential applications in theranostic medicine.

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