Cationic gas-filled microbubbles for ultrasound-based nucleic acids delivery

Delalande, Anthony; Bastié, Colette; Pigeon, Lucie; Manta, Simona; Lebertre, Matthias; Mignet, Nathalie; Midoux, Patrick; Pichon, Chantal

doi:10.1042/bsr20160619

Cited by 36 publications

(35 citation statements)

References 102 publications

(123 reference statements)

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“…Ultrasound (US)mediated gene delivery has the potential to transfect tumor and stromal cells with genes encoding for immune-related cytokine and chemokine production, while simultaneously debulking the tumor. US enhances the permeability of surrounding cells, allowing targeted local drug and gene delivery through a method known as sonoporation (3)(4)(5). Sonoporation is defined as the use of US to introduce pores in cell membranes.…”

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confidence: 99%

“…Creation of a low-cost, efficient, site-specific, and nontoxic nonviral gene transduction method remains a grand challenge. In recent years, sonoporation has emerged as a promising nonviral delivery method (3)(4)(5) and is endowed with the advantages of US (safety, ease of use, cost effectiveness, and clinical availability). Here, microbubble (MB) contrast agents, composed of a gas core and a stabilizing shell, are used to transiently form pores in the cell membrane and facilitate transmembrane transport of drugs and genes (17)(18)(19).…”

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confidence: 99%

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Low-frequency ultrasound-mediated cytokine transfection enhances T cell recruitment at local and distant tumor sites

Ilovitsh

Feng

Foiret

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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Robust cytotoxic T cell infiltration has proven to be difficult to achieve in solid tumors. We set out to develop a flexible protocol to efficiently transfect tumor and stromal cells to produce immune-activating cytokines, and thus enhance T cell infiltration while debulking tumor mass. By combining ultrasound with tumor-targeted microbubbles, membrane pores are created and facilitate a controllable and local transfection. Here, we applied a substantially lower transmission frequency (250 kHz) than applied previously. The resulting microbubble oscillation was significantly enhanced, reaching an effective expansion ratio of 35 for a peak negative pressure of 500 kPa in vitro. Combining low-frequency ultrasound with tumor-targeted microbubbles and a DNA plasmid construct, 20% of tumor cells remained viable, and ∼20% of these remaining cells were transfected with a reporter gene both in vitro and in vivo. The majority of cells transfected in vivo were mucin 1+/CD45−tumor cells. Tumor and stromal cells were then transfected with plasmid DNA encoding IFN-β, producing 150 pg/106cells in vitro, a 150-fold increase compared to no-ultrasound or no-plasmid controls and a 50-fold increase compared to treatment with targeted microbubbles and ultrasound (without IFN-β). This enhancement in secretion exceeds previously reported fourfold to fivefold increases with other in vitro treatments. Combined with intraperitoneal administration of checkpoint inhibition, a single application of IFN-β plasmid transfection reduced tumor growth in vivo and recruited efficacious immune cells at both the local and distant tumor sites.

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confidence: 99%

mentioning

confidence: 99%

Low-frequency ultrasound-mediated cytokine transfection enhances T cell recruitment at local and distant tumor sites

Ilovitsh

Feng

Foiret

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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“…Zhao et al (2018) reported that low-frequency ultrasound combined with microbubbles increased the transfection efficiency of siRNA (4 times) and porphyrin uptake (8 times) in MCF-7 (a human breast cancer cell line, estrogen receptor positive (ER + )), and inhibited ER + breast cancer cells more effectively, showing a good synergistic effect. Delalande et al (2017) reported that low-frequency ultrasound combined with microbubbles could effectively transfer plasmid DNA (pDNA), mRNA, or siRNA.…”

Section: Mediating Gene-targeted Therapy As a Vector For Improving Thmentioning

confidence: 99%

Advances in low-frequency ultrasound combined with microbubbles in targeted tumor therapy

Wang

Zheng

2019

J. Zhejiang Univ. Sci. B

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The development of low-frequency ultrasound imaging technology and the improvement of ultrasound contrast agent production technology mean that they play an increasingly important role in tumor therapy. The interaction between ultrasound and microbubbles and their biological effects can transfer and release microbubbles carrying genes and drugs to target tissues, mediate the apoptosis of tumor cells, and block the embolization of tumor microvasculature. With the optimization of ultrasound parameters, the development of targeted microbubbles, and the emergence of various composite probes with both diagnostic and therapeutic functions, low-frequency ultrasound combined with microbubble contrast agents will bring new hope for clinical tumor treatment.

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“…Both Definity and Optison have a neutral surface charge, and the latter requires minimal activation before use. Newer experimental cationic microbubble solutions are available that allow DNA-microbubble coupling, which can potentially increase the efficacy of sonoporation 31 .…”

Section: Introductionmentioning

confidence: 99%

Nonviral ultrasound-mediated gene delivery in small and large animal models

et al. 2019

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Ultrasound-mediated gene delivery (sonoporation) is a minimally invasive, nonviral and clinically translatable method of gene therapy. This method offers a favorable safety profile over that of viral vectors and is less invasive as compared with other physical gene delivery approaches (e.g., electroporation). We have previously used sonoporation to overexpress transgenes in different skeletal tissues in order to induce tissue regeneration. Here, we provide a protocol that could easily be adapted to address various other targets of tissue regeneration or additional applications, such as cancer and neurodegenerative diseases. This protocol describes how to prepare, conduct and optimize ultrasound-mediated gene delivery in both a murine and a porcine animal model. The protocol includes the preparation of a microbubble-DNA mix and in vivo sonoporation under ultrasound imaging. Ultrasound-mediated gene delivery can be accomplished within 10 min. After DNA delivery, animals can be followed to monitor gene expression, protein secretion and other transgene-specific outcomes, including tissue regeneration. This procedure can be accomplished by a competent graduate student or technician with prior experience in ultrasound imaging or in performing in vivo procedures.

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Cationic gas-filled microbubbles for ultrasound-based nucleic acids delivery

Cited by 36 publications

References 102 publications

Low-frequency ultrasound-mediated cytokine transfection enhances T cell recruitment at local and distant tumor sites

Low-frequency ultrasound-mediated cytokine transfection enhances T cell recruitment at local and distant tumor sites

Advances in low-frequency ultrasound combined with microbubbles in targeted tumor therapy

Nonviral ultrasound-mediated gene delivery in small and large animal models

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