Team VSAT - Laboratoire de Conception et Application de Molécules Bioactives


           Membres de l'équipe

          Luc LEBEAU (DR CNRS)
          Françoise PONS (PU)
          Anne CASSET (MCU)
          Carole RONZANI (MCU)
          Émilie SICK (MCU)  

          Ezeddine HARMOUCH (post-doctorant)
          Fareeha BATOOL (ATER)
          Samuel ARCA (doctorant)
          Thomas SCHOEPS (TCN, CDD)
          Manon PLUMAIL (IE, CDD)
          Jérémy Morel (M2)
          Maya Yven (M2)
          Fanny Burger (M1)

L'équipe VSAT fait partie de la Fondation pour la Recherche en Chimie et de l'Institut Thématique Interdisciplinaire (ITI) InnoVec. Ses activités sont principalement orientées vers le design et l’étude de systèmes lipidiques et nanoparticulaires avec, en ligne de mire, le développement de vecteurs non-viraux pour la thérapie génique. Composée de chimistes et de biologistes toxicologues, VSAT intègre les problématiques liées à la sécurité des systèmes qu’elle développe, dès leur conception et tout au long des processus d’optimisation. Ceci passe, notamment, par des études fondamentales sur la toxicité des systèmes nanoparticulaires et fait appel à une démarche expérimentale à la fois in vitro et in vivo.

Le développement spécifique de vecteurs permettant la délivrance simultanée de plusieurs agents thérapeutiques (un gène "médicament" et un agent de chimiothérapie conventionnel) et offrant la possibilité de mettre en œuvre deux modalités d’imagerie (par fluorescence et par résonance magnétique-IRM) est également activement poursuivi. L’objectif est de concevoir des agents théranostiques offrant les avantages complémentaires, en imagerie, de la sensibilité (fluorescence) et de la résolution spatiale et de la pénétration tissulaire (IRM).

D’autres travaux visent plus précisément des applications dans le traitement des pathologies pulmonaires (asthme, bronchopneumopathie chronique obstructive ou BPCO-maladie du fumeur, cancer du poumon…), avec une approche impliquant l’administration locale d’acides nucléiques thérapeutiques dans le poumon. Ceci impose une prise en compte des particularités de l’épithélium pulmonaire, notamment de la présence de mucus qui protège cet épithélium et limite l’efficacité des traitements. Les stratégies développées passent par l’élaboration de vecteurs dotés de propriétés mucolytiques intrinsèques et capables de moduler les propriétés viscoélastiques du mucus.

Mots-clés: vecteurs, nanoparticules, (nano)toxicologie, thérapie génique, agents théranostiques

Projets en cours

Publications

Surface charge influences protein corona, cell uptake and biological effects of carbon dots. Arezki, Y.; Delalande, F.; Schaeffer, C.; Rapp, M.; Lebeau, L.; Pons, F.; Ronzani, C. Nanoscale 2022, 14, 14695.
Cationic carbon nanoparticles induce inflammasome-dependent pyroptosis in macrophages via lysosomal dysfunction. Arezki, Y.; Rapp, M.; Lebeau, L.; Ronzani, C.; Pons, F. Front. Toxicol. 2022, 4, 925399.
Mucus producing epithelial models for investigating the activity of gene delivery systems in the lung. Sonntag, T.; Rapp, M.; Didier, P.; Lebeau, L.; Pons, F. Casset, A. Int. J. Pharm. 2022, 614, 121423.
A co-culture model of the human respiratory tract to discriminate the toxicological profile of cationic nanoparticles according to their surface charge density. Arezki, Y.; Cornacchia, J.; Rapp, M.; Lebeau, L.; Pons, F.; Ronzani, C. Toxics 2021, 9, 210.
The pH-induced specific area changes of unsaturated lipids deposited onto a bubble interface. Anton, N.; Pierrat, P.; Brou, G. A.; Gbassi, G. K.; Omran, Z.; Lebeau,L.; Vandamme, T. F.; Bouriat, P. Langmuir 2021, 37, 2586-2595.
Combined in vitro and in vivo approaches to propose a putative adverse outcome pathway for acute lung inflammation induced by nanoparticles: a study on carbon dots. Weiss, M.; Fan, J.; Claudel, M.; Lebeau, L.; Pons, F.; Ronzani, C. Nanomaterials 2021, 11, 180.
Density of surface charge is a more predictive factor of the toxicity of cationic nanoparticles than zeta potential. Weiss, M.; Fan, J.; Claudel, M.; Sonntag, T.; Didier, P.; Ronzani, C.; Lebeau, L.; Pons, F. J Nanobiotech 2021, 19, 5.
Biomaterial-assisted gene therapy for translational approaches to treat musculoskeletal disorders. Venkatesan, J.K.; Rey-Rico, A.; Meng, W.; Cai, X.; Pons, F.; Lebeau, L.; Migonney, V.; Madry, H.; Cucchiarini, M. Mater Today Adv 2021, 9, 100126.
Dual gene delivery reagents from antiproliferative alkyphospholipids for combined antitumor therapy. Gaillard, B.; Remy, J.-S.; Pons, F.; Lebeau, L. Front Chem 2020, 8, 581260.
Synthesis and evaluation of antitumor alkylphospholipid prodrugs. Gaillard B, Remy J-S, Pons F, Lebeau L. Pharm Res 2020, 37, 106.
rAAV-mediated overexpression of SOX9 and TGF-b via carbon dot-guided vector delivery enhances the biological activities in human bone marrow-derived mesenchymal stromal cells. Meng W, Rey-Rico A, Claudel M, Schmitt G, Speicher-Mentges S, Pons F, Lebeau L, Venkatesan JK, Cucchiarini M. Nanomaterials 2020, 10, 855.
Erufosine (ErPC3) cationic prodrugs as dual gene delivery reagents for combined antitumor therapy. Gaillard B, Seguin C, Remy JS, Pons F, Lebeau L. Chem-Eur J 2019, 25,15662-15679.
Physicochemical characteristics that affect carbon dot safety: Lessons from a comprehensive study on a nanoparticle library. Fan J, Claudel M, Ronzani C, Arezki Y, Lebeau L, Pons F. Int J Pharm 2019, 118521.
Effects of imidazoline-like drugs on liver and adipose tissues, and their role in preventing obesity and associated cardio-metabolic disorders. Aubertin G, Weiss M, Traversi F, Benameur D, Choquet P, Dali-Youcef N, Pons F, Sigrist S, Greney H, Monassier L, Bousquet P, Niederhoffer N. Int J Obes 2019.
Influence of carbonization conditions on luminescence and gene delivery properties of nitrogen-doped carbon dots. Claudel M, Fan J, Rapp M, Pons F, Lebeau L. RSC Adv 2019, 9:3493-3502.
Macrophage functionality and homeostasis in response to oligoethyleneglycol-coated IONPs: Impact of a dendritic architecture. Casset A, Jouhannaud J, Garofalo A, Spiegelhalter C, Nguyen DV, Felder-Flesch D, Pourroy G, Pons F. Int J Pharm 2019, 556:287-300.
Lysosome mediates toxicological effects of polyethyleneimine-based cationic carbon dots. Ronzani C, Van Belle C, Didier P, Spiegelhalter C, Pierrat P, Lebeau L, Pons F. J Nanopart Res 2019, 21:4.
Encapsulation of S-nitrosoglutathione: a transcriptomic validation. Safar R, Houlgatte R, Le Faou A, Ronzani C, Wu W, Ferrari L, Dubois-Pot-Schneider H, Rihn BH, Joubert O. Drug Dev Ind Pharm 2018, 17:1-28.
High-frequency stimulation of normal and blind mouse retinas Using TiO₂ nanotubes. Ronzani C, Cottineau T, Gonzalez-Valls I, Keller V, Picaud S, Keller N, Roux MJ. Adv Funct Mater 2018, 28:1804639.
Enhanced gene delivery to the lung using biodegradable polyunsaturated cationic phosphatidylcholine-detergent conjugates. Pierrat P, Kereselidze D, Lux M, Lebeau L, Pons F. Int J Pharm 2016, 511:205-218.
DOPC-Detergent conjugates: Fusogenic carriers for improved in vitro and in vivo gene delivery. Pierrat P, Casset A, Kereselidze D, Lux M, Pons F, Lebeau L. Macromol Biosci 2016, 7:984-989.
Cationic DOPC-detergent conjugates for safe and efficient in vitroand in vivonucleic acid delivery. Pierrat P, Casset A, Didier P, Kereselidze D, Lux M, Pons F, Lebeau L. Chembiochem 2016, 17:1771-1783.
Structure tuning of cationic oligospermine-siRNA conjugates for carrier-free gene silencing. Nothisen M, Bagilet J, Behr J-P, Remy J-S, Kotera M. Mol Pharm 2016, 13:2718-2728.
Preparation of poly(ethylene imine) derivatives with precisely controlled molecular weight. Landa M, Kotera M, Remy J-S, Badi N. Eur Polym J 2016, 84:338-344.
Liposomal constructs for antitumoral vaccination by the nasal route. Kakhi Z, Frisch B, Heurtault B, Pons F. Biochimie 2016, 130:14-22.
How in vitro assays contribute to allergy diagnosis. Casset A, Khayath N, de Blay F. Curr Allergy Asthma Rep 2016, 16:82.
Efficient in vitro and in vivo pulmonary delivery of nucleic acid by carbon dot-based nanocarriers. Pierrat P, Wang R, Kereselidze D, Lux M, Didier P, Kichler A, Pons F, Lebeau L. Biomaterials 2015, 51:290-302.
Characterization of titratable amphiphiles in lipid membranes by fluorescence spectroscopy. Pierrat P, Lebeau L. Langmuir 2015, 31:12362-12371.
Airway administration of a highly versatile peptide-based liposomal construct for local and distant antitumoral vaccination.Kakhi Z, Frisch B, Bourel-Bonnet L, Hemmerle J, PonsF, Heurtault B. Int J Pharm 2015, 496:1047-1056.
Synthesis of monodisperse sequence-coded polymers with chain lengths above DP100. Al Ouahabi A, Kotera M, Charles L, LutzJ-F. ACS Macro Lett 2015, 4:1077-1080.
Exposure to multi-walled carbon nanotubes results in aggravation of airway inflammation and remodeling and in increased production of epithelium-derived innate cytokines in a mouse model of asthma . Ronzani C, Casset A, Pons F. Arch Toxicol 2014, 88: 489-499.
Asthma management and inhalation techniques among community pharmacists in 2009: A comparison with the 1999 survey. Casset A, Meunier-Spitz M, Rebotier P, Lefevre H, Barth C, Heitz C, de Blay F. J Asthma 2014, 51: 964-973.
Phospholipid-detergent conjugates as novel tools for siRNA delivery. Pierrat P, Laverny G, Creusat G, Wehrung P, Strub J-M, VanDorsselaer A, Pons F, Zuber G, Lebeau L. Chem-Eur J 2013, 19:2344-2355.
Identification of Der p 23, a peritrophin-like protein, as a new major Dermatophagoides pteronyssinus allergen associated with the peritrophic matrix of mite fecal pellets. Weghofer M, Grote M, Resch Y, Casset A, Kneidinger M, Kopec J, Thomas WR, Fernandez-Caldas E, Kabesch M, Ferrara R, Mari A, Purohit A, Pauli G, Horak F, Keller W, Valent P, Valenta R, Vrtala S. J Immunol 2013, 190:3059-3067.
A study of insoluble monolayers by deposition at a bubble interface. Anton N, Pierrat P, Lebeau L, Vandamme TF, Bouriat P Soft Matter 2013, 9:10081-10091.
Nonallergic airway hyperresponsiveness and allergen-specific IgE levels are the main determinants of the early and late asthmatic response to allergen. Barnig C, Purohit A, Casset A, Sohy C, Lieutier-Colas F, Sauleau E, de Blay F. J Invest Allergol Clin Immunol 2013, 23:267-274.
Indoor dust and air concentrations of endotoxin in urban and rural environments. Barnig C, Reboux G, Roussel S, Casset A, Sohy C, Dalphin J-C, de Blay F. Lett Appl Microbiol 2013, 56:161-167.
A dynamic system for single and repeated exposure of airway epithelial cells to gaseous pollutants. Kastner PE, Le Calvé S, Zheng W, Casset A, Pons F. Toxicol in Vitro 2013, 27:632-640.
Immunomodulatory properties of multi-walled carbon nanotubes in peripheral blood mononuclear cells from healthy subjects and allergic patients. Laverny G, Casset A, Purohit A, Schaeffer E, Spiegelhalter C, de Blay F, Pons F. Toxicol Lett 2013, 217:91-101.
Monolayer two-dimensional crystallization of membrane proteins. Lebeau L, Venien-Bryan C. Methods Mol Biol 2013, 955:59-71.
Cell-penetrating cationic siRNA and lipophilic derivatives efficient at nanomolar concentrations in the presence of serum and albumin. Perche P, Nothisen M, Bagilet J, Behr J-P, Kotera M, Remy J-S. J Control Release 2013, 170:92-98.
Bioresponsive deciduous-charge amphiphiles for liposomal delivery of DNA and siRNA. Pierrat P, Kereselidze D, Wehrung P, Zuber G, Pons F, Lebeau L. Pharm Res 2013, 30:1362-1379.
Respiratory allergens and asthma exacerbation. Barnig C, CassetA. Rev Mal Respir 2012, 29:810-819.
The peroxisome proliferator-activated receptor alpha agonist fenofibrate decreases airway reactivity to methacholine and increases endothelial nitric oxide synthase phosphorylation in mouse lung. Becker J, Delayre-Orthez C, Frossard N, Pons F. Fund Clin Pharmacol 2012, 26:340-346.
Varying allergen composition and content affects the in vivo allergenic activity of commercial Dermatophagoides pteronyssinus extracts. Casset A, Mari A, Purohit A, Resch Y, Weghofer M, Ferrara R, Thomas WR, Alessandri C, Chen K-W, de Blay F, Valenta R, Vrtala S. Int Arch Allergy Immunol 2012, 159:253-262.
The cofactors of respiratory allergy. de Blay F, Lutz C, Casset A, Barnig C. Rev Fr Allergol 2012, 52:444-447.
A cationic phospholipid-detergent conjugate as a new efficient carrier for siRNA delivery. Pierrat P, Creusat G, Laverny G, Pons F, Zuber G, Lebeau L. Chem-Eur J 2012, 18:3835-3839.
Lung deposition and toxicological responses evoked by multi-walled carbon nanotubes dispersed in a synthetic lung surfactant in the mouse. Ronzani C, Spiegelhalter C, Vonesch J-L, Lebeau L, Pons F. Arch Toxicol 2012, 86:137-149.
Spleen-resident CD4(+) and CD4(-) CD8 alpha(-) dendritic cell subsets differ in their ability to prime invariant Natural Killer T lymphocytes. Bialecki E, Fernandez EM, Ivanov S, Paget C, Fontaine J, Rodriguez F, Lebeau L, Ehret C, Frisch B, Trottein F, Faveeuw C. Plos One 2011, 6:e26919.
Production of recombinant allergens. Casset A. Rev Fr Allergol 2011, 51:282-285.
Relationships between indoor allergens, sensitization, and allergic asthma and rhinitis symptoms. Casset A, Braun J-J. Rev Fr Allergol 2011, 51:104-110.
Formaldehyde interferes with airway epithelium integrity and functions in a dose- and time-dependent manner. Kastner PE, Casset A, Pons F Toxicol Lett 2011, 200:109-116.
Exposure of airway epithelial cells in culture to a mixture of gaseous pollutants: Impact on cell integrity. Kastner PE, Le Calvé S, Casset A, Zheng W, Pons F. Toxicol Lett 2011, 205:S123-S123.
Effects of carbon nanotubes on cytokine secretion by peripheral blood mononuclear cells from healthy subjects and allergic patients. Laverny G, Casset A, Purohit A, de Blay F, Pons F. Inflamm Res 2011, 60:175-176.
MTT, Npeoc-protected spermine, a valuable synthon for the solid phase synthesis of oligonucleotide oligospermine conjugates via guanidine linkers. Perche P, Kotera M, Remy J-S. Bioorg Med Chem 2011, 19:1972-1977.
Immunomodulatory properties of multi-walled carbon nanotubes in peripheral blood mononuclear cells. Pons F, Laverny G, Purohit A, De Blay F, Casset A. Toxicol Lett 2011, 205:S286-S287.
Effect of multi-walled carbon nanotubes on lung inflammation and systemic immune response in murine asthma models. Ronzani C, Casset A, Pons F. Toxicol Lett 2011, 205:S288-S288.
Predictor factors for airway responsiveness during bronchial allergen challenge tests: role of allergen-specific IgE levels, cutaneous allergen sensitivity and non-specific airway hyperresponsiveness. Barnig C, Purohit A, Casset A, Sohy C, Lieutier-Colas F, Meyer P, de Blay F. Allergy 2010, 65:20-20.
Relationships between indoor allergens, sensitization, and allergic asthma and rhinitis symptoms. Casset A, BraunJ-J. Rev Mal Respir 2010, 27:913-920.
Preparation and optical properties of novel 3-alkoxycarbonyl aza- and diazacoumarins. Féau C, Klein E, Kerth P, Lebeau L. Synth Commun 2010, 40:3033-3045.
Liposomes as delivery systems for nasal vaccination: Strategies and outcomes. Heurtault B, Frisch B, Pons F. Expert Opin Drug Deliv 2010, 7:829-844.
"HFP" Fluorinated cationic lipids for enhanced lipoplex stability and gene delivery. Klein E, Ciobanu M, Klein J, Machi J, Leborgne C, Vandamme T, Frisch B, Pons F, Kichler A, Zuber G, Lebeau L. Bioconjugate Chem 2010, 21:360-371.
Nucleic acid transfer with hemifluorinated polycationic lipids. Klein E, Leborgne C, Ciobanu M, Klein J, Frisch B, Pons F, Zuber G, Scherman D, Kichler A, Lebeau L Biomaterials 2010, 31:4781-4788.
Predictor factors for airway responsiveness during bronchial allergen challenge tests: Role of allergen-specific IgE levels, cutaneous allergen sensitivity and non-specific airway hyperresponsiveness. Barnig C, Purohit A, Casset A, Sohy C, Lieutier-Colas F, de Blay F. J Allergy Clin Immunol 2009, 123:S9-S9.
Increase in allergic sensitization. Casset A. Rev Fr Allergol 2009, 49:129-132.
Synthesis and characterization of coumarin-based europium complexes and luminescence measurements in aqueous media. Féau C, Klein E, Dosche C, Kerth P, Lebeau L. Org Biomol Chem 2009, 7:5259-5270.
Synthesis and properties of europium complexes derived from coumarin-derivatized azamacrocycles. Féau C, Klein E, Kerth P, Lebeau L. Synth Met 2009, 159:528-536.
Design of a liposomal candidate vaccine against Pseudomonas aeruginosa and its evaluation in triggering systemic and lung mucosal immunity. Heurtault B, Gentine P, Thomann J-S, Baehr C, Frisch B, Pons F. Pharm Res 2009, 26:276-285.
Cationic siRNAs provide carrier-free gene silencing in animal cells. Nothisen M, Kotera M, Voirin E, Remy J-S, Behr J-P. J Am Chem Soc 2009, 131:17730-17731.
Association of environmental cofactors and allergy. Pons F. Rev Fr Allergol 2009, 49:137-139.
Two-dimensional crystallisation of soluble protein complexes. Schultz P, Crucifix C, Lebeau L. Methods Mol Biol 2009, 543:353-367.

Recrutement

Quelques publications

Int J Pharm 2022 - Mucus producing epithelial models for investigating the activity of gene delivery systems in the lung.

Mater Today Adv 2021 - Biomaterial-assisted gene therapy for translational approaches to treat musculoskeletal disorders.

Front Chem 2020 - Dual gene delivery reagents from antiproliferative alkyphospholipids for combined antitumor therapy.

Chem-Eur J 2019 - Erufosine (ErPC3) cationic prodrugs as dual gene delivery reagents for combined antitumor therapy.

RSC Adv 2019 - Influence of carbonization conditions on luminescence and gene delivery properties of nitrogen-doped carbon dots.

Int J Pharm 2016 - Enhanced gene delivery to the lung using biodegradable polyunsaturated cationic phosphatidylcholine-detergent conjugates.

Biomaterials 2015 - Efficient in vitro and in vivo pulmonary delivery of nucleic acid by carbon dot-based nanocarriers.