The effects of albumin-coated microbubbles in DNA delivery mediated by therapeutic ultrasound

Duvshani-Eshet, Maayan; Adam, Dan; Machluf, Marcelle

doi:10.1016/j.jconrel.2006.02.013

Cited by 68 publications

(40 citation statements)

References 52 publications

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“…Our previous in vitro studies with Optison suggested that applying TUS for more than 15 min not only results in bubbles oscillation, but also induces cavitation. 20 Thus, it is possible that the application of TUS for 20 min or more is necessary for Optison to oscillate in the tumor resulting in much higher transfection efficiency and protein expression in the tumor.…”

Section: Discussionmentioning

confidence: 99%

Efficient transfection of tumors facilitated by long-term therapeutic ultrasound in combination with contrast agent: from in vitro to in vivo setting

Duvshani-Eshet

Machluf

2007

Cancer Gene Ther

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Therapeutic ultrasound (TUS) is a promising non-viral clinical approach for the delivery of genes. This study demonstrates the efficient delivery and localization of DNA in subcutaneous tumors facilitated by TUS application and examines the contribution of ultrasound contrast-agent (USCA) addition on transfection. The study addresses the importance of in vivo optimization when using long-term TUS and USCA based on data achieved in vitro. In vitro results showed that transfection of TrampC2 prostate cancer (Pca) cells using genes encoding for luciferase and green fluorescent protein was enhanced when DNA and Optison were added together and TUS was applied for 20 or 30 min. In vivo results showed that the highest transfection was achieved when Optison and DNA were co-injected intratumoraly, and TUS was applied for 20 min. Using Optison significantly increased protein distribution in the tumor. However, in vivo expression level was decreased by two and four fold at 7 and 14 days, respectively, post-TUS. The study establishes the potential of intratumoral delivery of DNA-Optison, followed by TUS as an effective, non-toxic, gene delivery method that could provide a safe, clinical alternative to current viral gene delivery approaches where short-term gene expression is needed.

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Section: Discussionmentioning

confidence: 99%

Efficient transfection of tumors facilitated by long-term therapeutic ultrasound in combination with contrast agent: from in vitro to in vivo setting

Duvshani-Eshet

Machluf

2007

Cancer Gene Ther

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“…31 Cavitation 32 has received the most attention, as many scientists have shown that the deliberate addition of echocontrast MCB 33,34 (used to enhance clinical ultrasound imaging) to the transfection medium before USE markedly increases subsequent transgene expression in vitro. 4,7,23,28,[35][36][37] Cavitation may be subdivided into two categories (see Figure 1):…”

Section: Technological Developments Have Increased the Efficiency Of mentioning

confidence: 99%

“…Recently, however, Machluf's group have reported that exposing baby hamster kidney cells to 0.16 MI 1 MHz ultrasound for 30 min in the presence of Optison MCB yielded more rhodamine-labelled plasmid in the nucleus compared with a 10 min exposure. 22,23 Whether this truly reflects a direct effect of prolonged USE upon nuclear uptake is difficult to assess as there was also more plasmid in the cytoplasm after USE for 30 min, which clearly altered the plasmid concentration gradient from cytoplasm to nucleus compared with a 10 min USE. Of note was the observation that some Optison MCB remained intact after 30 min, again consistent with, but not proof of, a role for stable cavitation in promoting UEGT.…”

Section: Multiple Biophysical Effects Of Ultrasound May Contribute Tomentioning

confidence: 99%

Gene therapy progress and prospects: Ultrasound for gene transfer

2007

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“…The use of ultrasound energy has intensively been studied for pDNA delivery [23][24][25][26][27][28][29][30]. Recently, ultrasound in combination with microbubbles has also been used in two reports to deliver naked siRNA [31,32].…”

Section: Introductionmentioning

confidence: 99%

Ultrasound assisted siRNA delivery using PEG-siPlex loaded microbubbles

Vandenbroucke

Lentacker

Demeester

et al. 2008

Journal of Controlled Release

110

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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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The effects of albumin-coated microbubbles in DNA delivery mediated by therapeutic ultrasound

Cited by 68 publications

References 52 publications

Efficient transfection of tumors facilitated by long-term therapeutic ultrasound in combination with contrast agent: from in vitro to in vivo setting

Efficient transfection of tumors facilitated by long-term therapeutic ultrasound in combination with contrast agent: from in vitro to in vivo setting

Gene therapy progress and prospects: Ultrasound for gene transfer

Ultrasound assisted siRNA delivery using PEG-siPlex loaded microbubbles

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