Microbubbles for Nucleic Acid Delivery in Liver Using Mild Sonoporation.

Ultrasound-mediated gene delivery is an interesting approach, which could help in increasing gene transfer in deep tissues. Moreover, it allows for performing experiments guided by the image to determine which elements are required. Microbubbles complexed with a eukaryotic expression cassette are excellent agents as they are responsive to ultrasounds and, upon oscillation, can destabilize membranes to enhance gene transfer.

Cationic microbubbles and antibiotic-free miniplasmid for sustained ultrasound-mediated transgene expression in liver.

Despite the increasing number of clinical trials in gene therapy, no ideal methods still allow non-viral gene transfer in deep tissues such as the liver. We were interested in ultrasound (US)-mediated gene delivery to provide long term liver expression. For this purpose, new positively charged microbubbles were designed and complexed with pFAR4, a highly efficient small length miniplasmid DNA devoid of antibiotic resistance sequence.

Evaluation of a new concept of immune-enhancing diet in a model of head-injured rat with infectious complications: A proof of concept study.

Immune-enhancing diet (IED) utilization in critically ill septic patients is still debated. A new concept of IED has been proposed combining extra glutamine sequentially with either antioxidants or other amino acids, in order to match patient requirements according to their response to injury. We evaluated whether this new IED elicits a more favorable response to stress when compared with two existing IEDs both enriched in arginine but with different levels of anti-oxidants, in a validated rat model combining head injury (HI) and infectious complications.

Characterization of Positively Charged Lipid Shell Microbubbles with Tunable Resistive Pulse Sensing (TRPS) Method: A Technical Note.

Microbubbles are polydisperse microparticles. Their size distribution cannot be accurately measured from the current methods used, such as optical microscopy, electrical sensing or light scattering. Indeed, these techniques present some limitations when applied to microbubbles, which prompted us to investigate the use of an alternative technique: tunable resistive pulse sensing (TRPS).

Magnetic and photoresponsive theranosomes: translating cell-released vesicles into smart nanovectors for cancer therapy.

Cell-released vesicles are natural carriers that circulate in body fluids and transport biological agents to distal cells. As nature uses vesicles in cell communication to promote tumor progression, we propose to harness their unique properties and exploit these biogenic carriers as Trojan horses to deliver therapeutic payloads to cancer cells. In a theranostic approach, cell-released vesicles were engineered by a top-down procedure from precursor cells, previously loaded with a photosensitizer and magnetic nanoparticles.

Mucosal imprinting of vaccine-induced CD8⁺ T cells is crucial to inhibit the growth of mucosal tumors.

Although many human cancers are located in mucosal sites, most cancer vaccines are tested against subcutaneous tumors in preclinical models. We therefore wondered whether mucosa-specific homing instructions to the immune system might influence mucosal tumor outgrowth. We showed that the growth of orthotopic head and neck or lung cancers was inhibited when a cancer vaccine was delivered by the intranasal mucosal route but not the intramuscular route.

Arginine reduces bacterial invasion in rats with head injury: an in vivo evaluation by bioluminescence.

Objectives: The benefit of arginine in intensive care unit patients with severe sepsis is still controversial. An excessive supply of arginine could lead to an overproduction of nitric oxide and could be responsible for septic shock and multiorgan failure. However, this claim is not supported by any experimental or clinical data.

In vivo bioluminescent imaging of a new model of infectious complications in head-injury rats.

Infectious complications are responsible for 10-25% of mortality in head-injured patients. In the present work we developed a model of infectious complications in head-injury rats using Escherichia coli (E. coli) with a stable copy of the lux operon, and monitored the infection in vivo by optical imaging.

A comprehensive study in triblock copolymer membrane interaction.

Poloxamers are triblock copolymers made of poly(ethylene glycol)-(poly(propylene glycol))-poly(ethylene glycol). They have been shown to enhance gene transfer in the muscle, and co-administration of polymers and DNA appeared to be crucial to obtain this effect. It is questionable then if some interaction occurs between polymers and DNA.

Ultrasound-assisted microbubbles gene transfer in tendons for gene therapy.

Our study aimed at evaluating the use of ultrasound-assisted microbubbles gene transfer in mice Achilles tendons. Using a plasmid encoding luciferase gene, it was found that an efficient and stable gene expression for more than two weeks was obtained when tendons were injected with 10 microg of plasmid in the presence of 5x10(5) BR14 microbubbles with the following acoustic parameters: 1 MHz, 200 kPa, 40% duty cycle and 10 min of exposure time. The rate of gene expression was 100-fold higher than that obtained with naked plasmid injected alone without ultrasound or with ultrasound in absence of microbubbles.

Optimisation of intradermal DNA electrotransfer for immunisation.

The development of DNA vaccines requires appropriate delivery technologies. Electrotransfer is one of the most efficient methods of non-viral gene transfer. In the present study, intradermal DNA electrotransfer was first optimised.

Plasmid DNA electrotransfer for intracellular and secreted proteins expression: new methodological developments and applications.

In vivo electrotransfer is a physical method of gene delivery in various tissues and organs, relying on the injection of a plasmid DNA followed by electric pulse delivery. The importance of the association between cell permeabilization and DNA electrophoresis for electrotransfer efficiency has been highlighted. In vivo electrotransfer is of special interest since it is the most efficient non-viral strategy of gene delivery and also because of its low cost, easiness of realization and safety.

Applications of plasmid electrotransfer.

The use of electric pulses to transfect cells has recently been extended to show the utility of this procedure in vivo. Electrotransfer has been performed in vivo on several tissue types including skin, blood vessels, liver, tumor, muscle, cornea, brain and spleen. The most widely targeted tissue has been skeletal muscle.