Non-invasive quantitative imaging of hepatocellular carcinoma growth in mice by micro-CT using liver-targeted iodinated nano-emulsions

Hepatocellular carcinoma (HCC) is the only cancer for which non-invasive diagnosis is recognized by international guidelines. Contrast agent free ultrasound imaging, computed tomography (CT) and/or magnetic resonance imaging are techniques used for early detection and confirmation. Clinical evidence depicts that CT is 30% less precise as compared to MRI for detection of small tumors. In our work, we have reported some novel tools that can enhance the sensitivity and precision of CT applied to preclinical research (micro-CT). Our system, containing non-toxic nano-droplets loaded with iodine has high contrasting properties, liver and hepatocyte specificity and strong liver persistence. Micro-CT was performed on HCC model implanted in nude mice by intrahepatic injection. Contrast agent was administrated intravenously. This method allows an unprecedented high precision of detection, quantitative measurement of tumor volume and quantitative follow-up of the tumor development.PMC565532

Do iodinated nano-emulsions designed for preclinical vascular imaging alter the vascular reactivity in rat aorta?

This study proposes a new methodology to evaluate the putative consequences of the long-lasting circulation in the blood pool of nanoparticulate systems widely used in nanomedicine, Indeed, the blood pool contrast agent for micro-computed tomography, i.e. iodinated nano-emulsions, have recently been developed, for their great potential in medical applications such as advanced diagnosis, image-guided surgery, personalized medicine or theragnostics. Stealth nanoparticles exhibit a low recognition by the reticuloendothelial system, resulting in a prolonged circulation in the bloodstream and long-lasting contact with the endothelium. Therefore, the aim of the present study is to determine whether this prolonged interaction could induce an alteration of the vascular reactivity in rat aorta. The Iodinated nano-emulsions were intravenously injected in anesthetized rats. After 1h of contrast agent circulation in the blood pool, the thoracic aorta was removed for the study of vascular reactivity. These animals were compared with control (untreated) rats and a third group of rats receiving an injection of phosphate buffered saline (i.e. dispersing phase of the nano-emulsions). Phenylephrine-induced concentration-dependent contractions of the isolated rat thoracic aorta were not modified whatever the group. Sodium nitroprusside (a nitric oxide (NO) donor)-induced relaxations of endothelium-denuded aorta were also unaltered in response to the different administrations. In contrast, in comparison with control animals, endothelium-dependent NO-mediated relaxations to acetylcholine were significantly impaired in thoracic aorta from PBS-treated rats, but not in animals receiving the iodinated nano-emulsion. In addition, neither isoprenaline-induced nor levcromakalim-induced relaxations were modified in the aorta from the three groups of animals. These findings indicate that even with a long-lasting residence time of the iodinated nano-emulsion in the blood flow, these iodinated nano-emulsions do not alter the vascular reactivity and thus can be used as contrast agent for preclinical vascular imaging on small laboratory animals

Functionalization of nano-emulsions with an amino-silica shell at the oil-water interface

Nano-emulsions are very promising nano-carriers with high potential for loading lipophilic drugs. However, the surface of oil nano-droplets is a dynamic oil/water interface stabilized by surfactants, and its chemical modification to graft ligands is highly challenging. In this study we developed a new protocol for modification of the nano-droplets surface through a silica shell terminated by amine functions. It enabled preparation of nanocapsules of 65, 85 and 120 nm diameters with a surface coverage of ca. 2 amino groups per nm(2). The nanocapsule surface was then functionalized (41% efficiency) by a model fluorescent ligand (coumarin blue) with a carboxylic function. The evidence for the successful grafting was provided by spectrofluorometry, Forster resonance energy transfer, atomic force microscopy coupled with fluorescence imaging and fluorescence correlation spectroscopy. This simple protocol for surface functionalization of the liquid/liquid interface of lipid droplets may constitute a real advance regarding potential applications that need efficient decoration of droplets with ligands

Biodistribution of x-ray iodinated contrast agent in nano-emulsions is controlled by the chemical nature of the oily core

In this study, we investigated the role of the chemical nature of the oil droplet core of nano-emulsions used as contrast agents for X-ray imaging on their pharmacokinetics and biodistribution. To this end, we formulated PEGylated nano-emulsions with two iodinated oils (i.e., iodinated monoglyceride and iodinated castor oil) and compared them with another iodinated nano-emulsion based on iodinated vitamin E. By using dynamic light scattering and transmission electron microscopy, the three iodinated nano-emulsions were found to exhibit comparable morphologies, size, and surface composition. Furthermore, they were shown to be endowed with very high iodine concentration, which leads to stronger X-ray attenuation properties as compared to the commercial iodinated nano-emulsion Fenestra VC. The three nano-emulsions were i.v. administered in mice and monitored by microcomputed tomography (micro-CT). They showed high contrast enhancement in blood with similar half-life around 6 h but very different accumulation sites. While iodinated monoglycerides exhibited low accumulation in liver and spleen, high accumulation in spleen was observed for iodinated castor oil and in liver for vitamin E. These data clearly highlighted the important role of the oil composition of the nano-emulsion core to obtain strong X-ray contrast enhancement in specific targets such as liver, spleen, or only blood. These differences in biodistribution were partly attributed to differences in the uptake of the nanodroplets by the macrophages in vitro. Another key feature of these nano-emulsions is their long half-elimination time (several weeks), which offers sufficient retention for micro-CT imaging. This work paves the way for the design of nanoparticulate contrast agents for X-ray imaging of selected organs

Improved size-tunable preparation of polymeric nanoparticles by microfluidic nanoprecipitation

International audienceSize-tunable polymeric nanoparticles have been successfully produced by a microfluidic-assisted nanoprecipitation process. A multilamination micromixer has been chosen to fabricate continuously nanoparticles of methacrylic polymers. Various operating conditions, such as the polymer concentration, the amount of non-solvent and the characteristics of the raw polymer (molecular weight and architecture: linear vs. branched) have been investigated. Their influences on the final particle size, ranging from 76 to 217 nm, have been correlated to the mechanisms leading to the formation of nanoparticles. In this type of microfluidic device, mixing mainly operates by diffusion mass transfer, helped by hydrodynamic focusing. The effect of micromixing on the size of particles has also been shown experimentally and supported by a computational fluid dynamics (CFD) study. A mixing criterion has been defined and numerically calculated to corroborate the effect of the flow rate of polymer solution on the particles size. An increase in the polymer solution flow rate increases the value of this mixing criterion, resulting in smaller nanoparticles

European survey on criteria of aesthetics for periodontal evaluation: The ESCAPE study

International audienc

Deciphering host migrations and origins by means of their microbes

Mitochondrial DNA and microsatellite sequences are powerful genetic markers for inferring the genealogy and the population genetic structure of animals but they have only limited resolution for organisms that display low genetic variability due to recent strong bottlenecks. An alternative source of data for deciphering migrations and origins in genetically uniform hosts can be provided by some of their microbes, if their evolutionary history correlates closely with that of the host. In this review, we first discuss how a variety of viruses, and the bacterium Helicobacter pylori , can be used as genetic tracers for one of the most intensively studied species, Homo sapiens. Then, we review statistical problems and limitations that affect the calculation of particular population genetic parameters for these microbes, such as mutation rates, with particular emphasis on the effects of recombination, selection and mode of transmission. Finally, we extend the discussion to other host parasite systems and advocate the adoption of an integrative approach to both sampling and analysis