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Lipoplex‐Loaded Microbubbles for Gene Delivery: A Trojan Horse Controlled by Ultrasound

2007; Wiley; Volume: 17; Issue: 12 Linguagem: Inglês

10.1002/adfm.200700106

1616-3028

Ine Lentacker, Stefaan C. De Smedt, J. Demeester, Veerle Van Marck, Marc Bracke, Niek N. Sanders,

Ultrasound and Cavitation Phenomena

Abstract Cationic poly(ethylene glycol)ylated (PEGylated) liposomes are one of the most important gene transfer reagents in non‐viral gene therapy. However, the low transfection efficiencies of highly PEGylated lipoplexes currently hamper their clinical use. Recently, ultrasound has been used in combination with microbubbles to enhance the uptake of genes in different cell types. However, the gene transfer efficiency still remains low in these experiments. To overcome the limitations of both techniques, we present the attachment of PEGylated lipoplexes to microbubbles via biotin–avidin–biotin linkages. Exposure of these lipoplex‐loaded microbubbles to ultrasound results in the release of unaltered lipoplexes. Furthermore, these lipoplex‐loaded microbubbles exhibit much higher transfection efficiencies than “free” PEGylated lipoplexes or naked plasmid DNA (pDNA) when combined with microbubbles and ultrasound. Interestingly, the lipoplex‐loaded microbubbles only transfect cells when exposed to ultrasound, which is promising for space‐ and time‐controlled gene transfer. Finally, this novel Trojan‐horse‐like concept can also be exploited to achieve the ultrasound‐triggered release of nanoparticles containing other therapeutic agents such as anticancer drugs.