Actualités

Un article intitulé "Rapamycin-loaded Poly(lactic-co-glycolic) acid nanoparticles: Preparation, characterization, and in vitro toxicity study for potential intra-articular injection" vient de paraître dans "International Journal of Pharmaceutics"

Auteurs : Elise Pape, Marianne Parent, Astrid Pinzano, Anne Sapin-Minet, Christel Henrionnet, Pierre Gillet, Julien Scala-Bertola, Nicolas Gambier

International Journal of Pharmaceutics, Elsevier, 2021, 609, pp.121198. https://doi.org/10.1016/j.ijpharm.2021.121198

Abstract : 

Osteoarthritis (OA) is the most common degenerative joint disease. Rapamycin is a potential candidate for OA treatment by increasing the autophagy process implicated in its physiopathology. To optimize Rapamycin profit and avoid systemic side effects, intra-articular (i.a.) administration appeared helpful. However, Rapamycin's highly hydrophobic nature and low bioavailability made it challenging to develop purpose-made drug delivery systems to overcome these limitations. We developed Rapamycin-loaded nanoparticles (NPs) using poly (lactic-co-glycolic acid) by emulsion/evaporation method. We evaluated these NPs' cytocompatibility towards cartilage (chondrocytes) and synovial membrane cells (synoviocytes) for a potential i.a. administration. The in vitro characterization of Rapamycin-loaded NPs had shown a suitable profile for an i.a. administration. In vitro biocompatibility of NPs was highlighted to 10 µM of Rapamycin for both synoviocytes and chondrocytes, but significant toxicity was observed with higher concentrations. Besides, synoviocytes are more sensitive to Rapamycin-loaded NPs than chondrocytes. Finally, we observed in vitro that an adapted formulated Rapamycin-loaded NPs could be safe at suitable i.a. injection concentrations. The toxic effect of Rapamycin encapsulated in these NPs on both articular cells was dose-dependent. After Rapamycin-loaded NPs i.a. administration, local retention, in situ safety, and systemic release should be evaluated with experimental in vivo models.

Un article intitulé "Recent progress in the toxicity of nitric oxide-releasing nanomaterials" vient de paraître dans "Materials Advances"

Auteurs : Joana Claudio Pieretti, Milena T Pelegrino, Ariane Boudier, Amedea Barozzi Seabra

Materials Advances, Royal Society of Chemistry, 2021, https://doi.org/10.1039/D1MA00532D

Abstract : 

Nitric oxide (NO) is a signaling molecule controlling important biological processes. Depending on its concentration, location and cellular environment, NO can have protective or toxic effects. As NO is a free radical, several classes of NO donors/generators have been prepared and combined with nanomaterials, in particular with polymeric nanoparticles. Engineered nanoparticles are attractive nanocarriers extensively used in biomedical applications, in particular in cancer biology due to their ability to promote a site-target therapeutic effect, with minimum side effects to health tissues. NO-releasing nanoparticles can have direct toxic effects to tumor cells, or it can promote cancer cells sensitization to traditional cancer treatments. The combination of NO-releasing nanoparticles with conventional anticancer therapies is a promising approach in the reversion of multidrug resistance (MDR) cells. This review presents and discusses the recent progress in the cytotoxicity (tumoral and non-tumoral cell lines) of NO-releasing polymeric and/or polymer-coated nanomaterials and the in vivo biocompatibility of NO-releasing nanoparticles. Moreover, the ability of these nanoparticles to combat MDR, their mechanisms of toxicity and drawbacks are also discussed.

Un article intitulé "The Impact of Multiple Functional Layers in the Structure of Magnetic Nanoparticles and Their Influence on Albumin Interaction" vient de paraître dans "International Journal of Molecular Sciences".

Auteurs : Pieretti, J.C.; Beurton, J.; Munevar, J.; Nagamine, L.C.C.M.; Le Faou, A.; Seabra, A.B.; Clarot, I.; Boudier, A.

Int. J. Mol. Sci. 2021, 22, 10477. https://doi.org/10.3390/ijms221910477

Abstract

In nanomedicine, hybrid nanomaterials stand out for providing new insights in both the diagnosis and treatment of several diseases. Once administered, engineered nanoparticles (NPs) interact with biological molecules, and the nature of this interaction might directly interfere with the biological fate and action of the NPs. In this work, we synthesized a hybrid magnetic nanostructure, with antibacterial and antitumoral potential applications, composed of a magnetite core covered by silver NPs, and coated with a modified chitosan polymer. As magnetite NPs readily oxidize to maghemite, we investigated the structural properties of the NPs after addition of the two successive layers using Mössbauer spectroscopy. Then, the structural characteristics of the NPs were correlated to their interaction with albumin, the major blood protein, to evidence the consequences of its binding on NP properties and protein retention. Thermodynamic parameters of the NPs–albumin interaction were determined. We observed that the more stable NPs (coated with modified chitosan) present a lower affinity for albumin in comparison to pure magnetite and magnetite/silver hybrid NPs. Surface properties were key players at the NP–biological interface. To the best of our knowledge, this is the first study that demonstrates a correlation between the structural properties of complex hybrid NPs and their interaction with albumin.

Jordan BEURTON soutiendra sa thèse de doctorat intitulée "Optimisation physico-chimique de films fonctionnalisés pour des applications cardiovasculaires" le vendredi 17 septembre à 13h30 dans la salle de réunion de l'équipe de recherche.

Le jury est composé de :

- M. Nicolas BLANCHEMAIN (Rapporteur, PR, U1008 INSERM, Faculté de Pharmacie de Lille, Lille)

- Mme Sophie DEMOUSTIER-CHAMPAGNE (Rapporteur, PR, IMCN/BSMA, Université Catholique de Louvain, Louvain-la-Neuve)

- Mme Corine GERARDIN (Examinateur, DR, Institut Charles Gerhardt, UMR 5253 CNRS, Université de Montpellier, Montpellier)

- M. Gregory FRANCIUS (Examinateur, DR, LCPME UMR 7564 CNRS, Université de Lorraine, Nancy)

- Mme Ariane BOUDIER (Examinateur, PR, EA 3452 CITHEFOR Université de Lorraine, Nancy, Directrice de thèse)

- M. Philippe LAVALLE (Examinateur, DR, U 1121 INSERM, Université de Strasbourg, Strasbourg, Co-directeur de thèse)

- M. Benoit FRISCH (Membre invité, DR, UMR7199 CNRS, Université de Strasbourg, Strasbourg)

- M. Raphaël DUVAL (Membre invité, PR, L2CM UMR 7053 CNRS, Université de Lorraine, Nancy)

Un nouvela article intitulé "Room-temperature growth of covalent organic framework as stationary phase for open-tubular capillary electrochromatography" vient de paraître dans "Analyst".

Auteurs : Qiaoyan Li, Zhengtao Li, Yuanyuan Fu, Igor Clarot, Ariane Boudier, Zilin Chen

Analyst, Royal Society of Chemistry, 2021, https://doi.org/10.1039/D1AN01402A

Abstract :

Covalent organic frameworks (COFs) is a class of porous materials with high surface area, high porosity, good stability and tunable structure that have been neatly used in the separation area. In this work, we have proposed the in-situ synthesis of a novel COF composed of 4,4',4''-(1,3,5-Triazine-2,4,6-triyl)trianiline (Tz) and 1,4-dihydroxyterephthalaldehyde (Da) onto the capillary inner surface for electrochromatographic separation. Fourier transform infrared spectroscopy (FT-IR), elemental analysis (EA) and scanning electron microscopy (SEM) have been facilitated to characterize the prepared capillary columns. The COF (TzDa) modified OT-CEC column exhibited satisfactory separation selectivity towards neutral compounds (such as chlorobenzenes and alkylbenzenes), acidic and basic compounds (such as phenols and anilines), food additives (vanillin and its analogues) and small biomolecules (such as amino acids and polypeptides). Furthermore, the TzDa modified capillary was quite stable and repeatable. The relative standard deviations for retention times of the test analytes (alkylbenzenes) were as follow: for intra-day (n = 3) runs (≤ 1.74%), inter-day (n = 3) runs (≤ 2.25%) and column to columns (n = 3) (≤ 4.83%). This new type of COF-based stationary phase has tremendous potential in separation science.

Le projet de recherche collaborative (PRC) SMILING a été sélectionné définitivement pour un financement par l'ANR.

Il s'agit d'un projet dont Caroline GAUCHER, MCF au sein du laboratoire, est partenaire.

Évaluation préclinique chez le gros animal d’un substitut vasculaire construit par ingénierie tissulaire à partir du cordon ombilical humain

Preclinical evaluation, in a big animal model, of a tissue-engineered vascular substitute derived from the human umbilical cord

SMall dIameter vascuLar cellularIzed humaN Graft (SMILING)

Porteur Pr V Decot, PU-PH (UTCT, CHRU Nancy)

Partenaires :

• Pr P Menu et Dr Reine El Omar (UMR 7365 IMoPA)
• Dr C Gaucher (EA 3452)
• Pr N Tran et Pr P Maureira (UMR_S 1116 DCAC, Ecole de Chirurgie de Nancy Lorraine)

Les maladies cardiovasculaires représentent 31% des décès mondiaux. Leur traitement chirurgical repose sur des greffes vasculaires afin de contourner une sténose. Bien que les vaisseaux autologues soient la règle d'or, la disponibilité limitée des greffes vasculaires de petit diamètre est un réel problème de santé publique. Nous avons mis au point un substitut vasculaire innovant de petit diamètre (SMILING), entièrement construit à partir du cordon ombilical humain : la matrice issue d'une artère ombilicale décellularisée, recouverte de gelée de Wharton et cellularisée avec des cellules souches mésenchymateuses. Pour envisager un essai clinique de phase I, ce projet vise à produire SMILING conformément aux normes françaises de bonnes pratiques de fabrication (BPF) imposées par l'ANSM et à le valider en tant que substitut lors d’un pontage coronarien chez le porc. Le projet «SMILING» développera un produit thérapeutique pour plusieurs applications possibles en médecine régénérative.

Cardiovascular disease accounts for 31% of global deaths. Their surgical treatment is based on vascular grafts in order to bypass stenosis. Although autologous vessels are the gold standard, the limited availability of small diameter vascular grafts is a real public health issue. We have developed an innovative small diameter vascular substitute (SMILING), entirely constructed from the human umbilical cord: the matrix resulting from a decellularized umbilical artery, covered with Wharton's jelly and cellularized with mesenchymal stem cells. To consider a phase I clinical trial, this project aims to produce SMILING in accordance with French standards of good manufacturing practices (GMP) imposed by the ANSM and to validate it as a substitute during coronary bypass surgery in pigs. The “SMILING” project will allow the development of a therapeutic product for several possible applications in regenerative medicine.

Nous avons le plaisir d'accueillir de nouveaux arrivants au sein de l'équipe de recherche :

- Jérémie Gouyon, MCU, Thématique de recherche : Caractérisation de nanoparticules et développement de méthodes analytiques

- Franceline REYNAUD, ATER en Pharmacie galénique, Thématique de recherche : Complexation de particules lipidiques avec l'ADN

- Diego Mauricio RAMOS, ATER en pharmacie galénique, Thématique de recherche : Emulsions lipidiques

Nous leur souhaitons la bienvenue.

Un article intitulé "Rubella epidemiology in the Central African Republic, 2015-2016 and molecular characterization of virus strains from 2008-2016" vient de paraître dans "International Journal of Infectious Diseases".

Auteurs : M. S. Pagonendji, I.Gouandkika-Vasilache, E. Charpentier, A. Sausy, A. Le Faou, R.E. Duval, J. M. Hübschen

Int J Infect Dis. 2021 Aug 24;S1201-9712(21)00684-6. doi: 10.1016/j.ijid.2021.08.050.

Abstract :

Objectives: Rubella cases in the Central African Republic (CAF) are currently identified during measles surveillance. This study aimed to investigate rubella epidemiology between 2015 and 2016 and to provide baseline genotype data for monitoring future rubella control efforts.

Methods: 831 measles IgM negative or equivocal sera from 2015/2016 were tested for rubella IgM antibodies and 350 rubella IgM positive sera collected between 2008 and 2016 were selected for PCR and sequencing.

Results: 411 of the 831 sera (49.5%) were rubella IgM positive and most cases (n=391, 95.1%) occurred between January and April. Most patients were between 5 and 9 years old (50.2%) and more than half of the rubella cases (56.7%) originated from the capital Bangui. Genotype information was obtained for 37 of the 350 selected rubella IgM-positive specimens, with the majority of the patients originating from Bangui (n=24, 64.9%) and sequences covering all years except 2009. Phylogenetic analysis identified genotypes 1E (n=12), 1G (n=5) and 2B (n=20), with 2B being detected from 2014 onwards.

Conclusions: Our study confirmed the important role of rubella as rash and fever disease in CAF and provided comprehensive data on rubella epidemiology and first information on rubella genotypes in the country.

Un article intitulé "Targeting the Angiotensin II Type 1 Receptor in Cerebrovascular Diseases: Biased Signaling Raises New Hopes" vient d'être publié dans l'issue spéciale "Molecular Vascular Physiology" du journal "International Journal of Molecular Sciences".

Auteurs : Céline Delaitre, Michel Boisbrun, Sandra Lecat, François Dupuis

Int. J. Mol. Sci. 2021, 22(13), 6738; https://doi.org/10.3390/ijms22136738

Abstract :

The physiological and pathophysiological relevance of the angiotensin II type 1 (AT1) G protein-coupled receptor no longer needs to be proven in the cardiovascular system. The renin–angiotensin system and the AT1 receptor are the targets of several classes of therapeutics (such as angiotensin converting enzyme inhibitors or angiotensin receptor blockers, ARBs) used as first-line treatments in cardiovascular diseases. The importance of AT1 in the regulation of the cerebrovascular system is also acknowledged. However, despite numerous beneficial effects in preclinical experiments, ARBs do not induce satisfactory curative results in clinical stroke studies. A better understanding of AT1 signaling and the development of biased AT1 agonists, able to selectively activate the β-arrestin transduction pathway rather than the Gq pathway, have led to new therapeutic strategies to target detrimental effects of AT1 activation. In this paper, we review the involvement of AT1 in cerebrovascular diseases as well as recent advances in the understanding of its molecular dynamics and biased or non-biased signaling. We also describe why these alternative signaling pathways induced by β-arrestin biased AT1 agonists could be considered as new therapeutic avenues for cerebrovascular diseases.

Un article intitulé " Electrically Switchable Nanolever Technology for the Screening of Metal-Chelating Peptides in Hydrolysates" vient d'être publié dans "Journal of Agricultural and Food Chemistry".

Auteurs : Sarah El Hajj, Cindy Tatiana Sepúlveda Rincón, Jean-Michel Girardet, Céline Cakir-Kiefer, Loic Stefan, José Edgar Zapata Montoya, Sandrine Boschi-Muller, Caroline Gaucher, Laetitia Canabady-Rochelle

J Agric Food Chem. 2021 Aug 11;69(31):8819-8827. doi: 10.1021/acs.jafc.1c02199.

Abstract

Metal-chelating peptides (MCP) are considered as indirect antioxidants due to their capacity to inhibit radical chain reaction and oxidation. Here, we propose a new proof of concept for the screening of MCPs present in protein hydrolysates for valorizing their antioxidant properties by using the emerging time-resolved molecular dynamics technology, switchSENSE. This method unveils possible interactions between MCPs and immobilized nickel ions using fluorescence and electro-switchable DNA chips. The switchSENSE method was first set up on synthetic peptides known for their metal-chelating properties. Then, it was applied to soy and tilapia viscera protein hydrolysates. Their Cu2+-chelation capacity was, in addition, determined by UV-visible spectrophotometry as a reference method. The switchSENSE method has displayed a high sensitivity to evidence the presence of MCPs in both hydrolysates. Hence, we demonstrate for the first time that this newly introduced technology is a convenient methodology to screen protein hydrolysates in order to determine the presence of MCPs before launching time-consuming separations.