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Ultrasound-responsive polymer-coated microbubbles that bind and protect DNA

(2006) LANGMUIR. 22(17). p.7273-7278
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Abstract
Ultrasound in combination with microbubbles has recently been considered by gene delivery scientists to be an interesting approach to enhance gene transfer into cells. Its low toxicity and simplicity to apply in vivo without major complications make this technology (sonoporation) especially attractive. Sonoporation of DNA has been evaluated in vivo by the injection of free plasmid DNA (pDNA) together with microbubbles (as used in diagnostic imaging) in the bloodstream. However, the in vivo gene-transfer efficiency in these experiments remained rather low. Both the enzymatic degradation of the injected pDNA as well as the low pDNA concentration in the neighborhood of sonoporated cell membranes may explain this low efficiency. Therefore, we developed polymer-coated microbubbles that can bind and protect the pDNA. Coating albumin-shelled microbubbles with poly(allylamine hydrochloride) (PAH) makes the surface charge of the microbubbles positive without drastically affecting the size distribution of the microbubbles, thereby not affecting the ultrasound responsiveness and injectability. The cationic coating allowed both to bind up to 0.1 pg of DNA per microbubble as well as to protect the bound DNA against nucleases. Finally, the PAH coating significantly increased the lifetime of the microbubbles (half-life approximately 7 h), making them more convenient for in vivo applications because more microbubbles are expected to reach the target organ. Binding and nuclease protection of DNA by polymer-coated diagnostic microbubbles has, to our knowledge, never been demonstrated. We conclude that these LbL-coated microbubbles might be significant in the further development of ultrasound-mediated gene delivery.

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Chicago
Lentacker, Ine, Bruno De Geest, Roosmarijn Vandenbroucke, Liesbeth Peeters, Jo Demeester, Stefaan De Smedt, and Niek Sanders. 2006. “Ultrasound-responsive Polymer-coated Microbubbles That Bind and Protect DNA.” Langmuir 22 (17): 7273–7278.
APA
Lentacker, I., De Geest, B., Vandenbroucke, R., Peeters, L., Demeester, J., De Smedt, S., & Sanders, N. (2006). Ultrasound-responsive polymer-coated microbubbles that bind and protect DNA. LANGMUIR, 22(17), 7273–7278.
Vancouver
1.
Lentacker I, De Geest B, Vandenbroucke R, Peeters L, Demeester J, De Smedt S, et al. Ultrasound-responsive polymer-coated microbubbles that bind and protect DNA. LANGMUIR. AMER CHEMICAL SOC; 2006;22(17):7273–8.
MLA
Lentacker, Ine, Bruno De Geest, Roosmarijn Vandenbroucke, et al. “Ultrasound-responsive Polymer-coated Microbubbles That Bind and Protect DNA.” LANGMUIR 22.17 (2006): 7273–7278. Print.
@article{346698,
  abstract     = {Ultrasound in combination with microbubbles has recently been considered by gene delivery scientists to be an interesting approach to enhance gene transfer into cells. Its low toxicity and simplicity to apply in vivo without major complications make this technology (sonoporation) especially attractive. Sonoporation of DNA has been evaluated in vivo by the injection of free plasmid DNA (pDNA) together with microbubbles (as used in diagnostic imaging) in the bloodstream. However, the in vivo gene-transfer efficiency in these experiments remained rather low. Both the enzymatic degradation of the injected pDNA as well as the low pDNA concentration in the neighborhood of sonoporated cell membranes may explain this low efficiency. Therefore, we developed polymer-coated microbubbles that can bind and protect the pDNA. Coating albumin-shelled microbubbles with poly(allylamine hydrochloride) (PAH) makes the surface charge of the microbubbles positive without drastically affecting the size distribution of the microbubbles, thereby not affecting the ultrasound responsiveness and injectability. The cationic coating allowed both to bind up to 0.1 pg of DNA per microbubble as well as to protect the bound DNA against nucleases. Finally, the PAH coating significantly increased the lifetime of the microbubbles (half-life approximately 7 h), making them more convenient for in vivo applications because more microbubbles are expected to reach the target organ. Binding and nuclease protection of DNA by polymer-coated diagnostic microbubbles has, to our knowledge, never been demonstrated. We conclude that these LbL-coated microbubbles might be significant in the further development of ultrasound-mediated gene delivery.},
  author       = {Lentacker, Ine and De Geest, Bruno and Vandenbroucke, Roosmarijn and Peeters, Liesbeth and Demeester, Jo and De Smedt, Stefaan and Sanders, Niek},
  issn         = {0743-7463},
  journal      = {LANGMUIR},
  language     = {eng},
  number       = {17},
  pages        = {7273--7278},
  publisher    = {AMER CHEMICAL SOC},
  title        = {Ultrasound-responsive polymer-coated microbubbles that bind and protect DNA},
  url          = {http://dx.doi.org/10.1021/la0603828},
  volume       = {22},
  year         = {2006},
}

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