Comparison of the Spatial Organization in Colorectal Tumors using Second-Order Statistics and Functional ANOVA

International audienceWe propose an automatic method to quantitatively describe the spatial organization governing populations of biological objects, such as cells, which exist in stationary histology images. This quantification is of prime importance when striving to compare different tumoral models in order to evaluate potential therapies. We compare two animal models of colorectal cancer. Our approach is based on the topographic map to automatically extract the location of the relevant biological objects. We describe their spatial organization along a continuous range of scales using second-order statistics. Using a functional analysis of variance test, we show that there are significant differences in these statistics depending on cancer model, and on the day after tumor implant

Positively charged microbubbles to target nucleic acid delivery with ultrasound

Congrès sous l’égide de la Société Française de Génie Biologique et Médical (SFGBM).National audienceNucleic acid delivery in vivo via physical means or non-viral vectors still need improvements in particular to reach deep tissues. Sonoporation is highly advantageous for this purpose as ultrasound can be focalised to a particular tissue leading to targeted gene delivery, without alteration of the environing tissues. Few examples of transfection using cationic microbubbles (MBs) and DNA have been reported. We ought to improve the existing systems by developing positively charged MBs able to oscillate in order to follow their fate in vivo and gain in understanding of the pharmacokinetic of the MBs, then target DNA delivery with ultrasound. After optimisation, we obtained MBs in the 1-3 !m range (98% below 10 !m) able to adsorb nucleic acid on their surface. In vitro parameters have been optimised to obtain in vitro transfection both with DNA and siRNA. The systemic injection in mice led to the observation of these MBs in the liver in less than 10 seconds. This investigation allows to address the key parameters to tentatively obtain reproducible gene transfection in vivo

AGuIX® from bench to bedside-Transfer of an ultrasmall theranostic gadolinium-based nanoparticle to clinical medicine

International audienceAGuIX® are sub-5 nm nanoparticles made of a polysiloxane matrix and gadolinium chelates. This nanoparticle has been recently accepted in clinical trials in association with radiotherapy. This review will summarize the principal preclinical results that have led to first in man administration. No evidence of toxicity has been observed during regulatory toxicity tests on two animal species (rodents and monkeys). Biodistributions on different animal models have shown passive uptake in tumours due to enhanced permeability and retention effect combined with renal elimination of the nanoparticles after intravenous administration. High radiosensitizing effect has been observed with different types of irradiations in vitro and in vivo on a large number of cancer types (brain, lung, melanoma, head and neck…). The review concludes with the second generation of AGuIX nanoparticles and the first preliminary results on human

Bioavailability of Polyphenol Liposomes: A Challenge Ahead

Dietary polyphenols, including flavonoids, have long been recognized as a source of important molecules involved in the prevention of several diseases, including cancer. However, because of their poor bioavailability, polyphenols remain difficult to be employed clinically. Over the past few years, a renewed interest has been devoted to the use of liposomes as carriers aimed at increasing the bioavailability and, hence, the therapeutic benefits of polyphenols. In this paper, we review the causes of the poor bioavailability of polyphenols and concentrate on their liposomal formulations, which offer a means of improving their pharmacokinetics and pharmacodynamics. The problems linked to their development and their potential therapeutic advantages are reviewed. Future directions for liposomal polyphenol development are suggested

Lipids for Nucleic Acid Delivery: Cationic or Neutral Lipoplexes, Synthesis, and Particle Formation

International audienc

Lipids for Nucleic Acid Delivery: Cationic or Neutral Lipoplexes, Synthesis, and Particle Formation

International audienc