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Ultrasound assisted siRNA delivery using PEG-siPlex loaded microbubbles

Roosmarijn Vandenbroucke (UGent) , Ine Lentacker (UGent) , Jo Demeester (UGent) , Stefaan De Smedt (UGent) and Niek Sanders (UGent)
(2008) JOURNAL OF CONTROLLED RELEASE. 126(3). p.265-273
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Abstract
Short interfering RNA (siRNA) attracts much attention for the treatment of various diseases. However, its delivery, especially via systemic routes, remains a challenge. Indeed, naked siRNAs are rapidly degraded, while complexed siRNAs massively aggregate in the blood or are captured by macrophages. Although this can be circumvented by PEGylation, we found that PEGylation had a strong negative effect on the gene silencing efficiency of siRNA-liposome complexes (siPlexes). Recently, ultrasound combined with microbubbles has been used to deliver naked siRNA but the gene silencing efficiency is rather low and very high amounts of siRNA are required. To overcome the negative effects of PEGylation and to enhance the efficiency of ultrasound assisted siRNA delivery, we coupled PEGylated siPlexes (PEG-siPlexes) to microbubbles. Ultrasound radiation of these microbubbles resulted in massive release of unaltered PEG-siPlexes. Interestingly, PEG-siPlexes loaded on microbubbles were able to enter cells after exposure to ultrasound, in contrast to free PEG-siPlexes, which were not able to enter cells rapidly. Furthermore, these PEG-siPlex loaded microbubbles induced, in the presence of ultrasound, much higher gene silencing than free PEG-siPlexes. Additionally, the PEG-siPlex loaded microbubbles only silenced the expression of genes in the presence of ultrasound, which allows space and time controlled gene silencing.

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Chicago
Vandenbroucke, Roosmarijn, Ine Lentacker, Jo Demeester, Stefaan De Smedt, and Niek Sanders. 2008. “Ultrasound Assisted siRNA Delivery Using PEG-siPlex Loaded Microbubbles.” Journal of Controlled Release 126 (3): 265–273.
APA
Vandenbroucke, Roosmarijn, Lentacker, I., Demeester, J., De Smedt, S., & Sanders, N. (2008). Ultrasound assisted siRNA delivery using PEG-siPlex loaded microbubbles. JOURNAL OF CONTROLLED RELEASE, 126(3), 265–273.
Vancouver
1.
Vandenbroucke R, Lentacker I, Demeester J, De Smedt S, Sanders N. Ultrasound assisted siRNA delivery using PEG-siPlex loaded microbubbles. JOURNAL OF CONTROLLED RELEASE. 2008;126(3):265–73.
MLA
Vandenbroucke, Roosmarijn, Ine Lentacker, Jo Demeester, et al. “Ultrasound Assisted siRNA Delivery Using PEG-siPlex Loaded Microbubbles.” JOURNAL OF CONTROLLED RELEASE 126.3 (2008): 265–273. Print.
@article{427482,
  abstract     = {Short interfering RNA (siRNA) attracts much attention for the treatment of various diseases. However, its delivery, especially via systemic routes, remains a challenge. Indeed, naked siRNAs are rapidly degraded, while complexed siRNAs massively aggregate in the blood or are captured by macrophages. Although this can be circumvented by PEGylation, we found that PEGylation had a strong negative effect on the gene silencing efficiency of siRNA-liposome complexes (siPlexes). Recently, ultrasound combined with microbubbles has been used to deliver naked siRNA but the gene silencing efficiency is rather low and very high amounts of siRNA are required. To overcome the negative effects of PEGylation and to enhance the efficiency of ultrasound assisted siRNA delivery, we coupled PEGylated siPlexes (PEG-siPlexes) to microbubbles. Ultrasound radiation of these microbubbles resulted in massive release of unaltered PEG-siPlexes. Interestingly, PEG-siPlexes loaded on microbubbles were able to enter cells after exposure to ultrasound, in contrast to free PEG-siPlexes, which were not able to enter cells rapidly. Furthermore, these PEG-siPlex loaded microbubbles induced, in the presence of ultrasound, much higher gene silencing than free PEG-siPlexes. Additionally, the PEG-siPlex loaded microbubbles only silenced the expression of genes in the presence of ultrasound, which allows space and time controlled gene silencing.},
  author       = {Vandenbroucke, Roosmarijn and Lentacker, Ine and Demeester, Jo and De Smedt, Stefaan and Sanders, Niek},
  issn         = {0168-3659},
  journal      = {JOURNAL OF CONTROLLED RELEASE},
  language     = {eng},
  number       = {3},
  pages        = {265--273},
  title        = {Ultrasound assisted siRNA delivery using PEG-siPlex loaded microbubbles},
  url          = {http://dx.doi.org/10.1016/j.jconrel.2007.12.001},
  volume       = {126},
  year         = {2008},
}

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