L’équipe INPACT développe, sur la base de concepts physico-chimiques et physiopathologiques, des systèmes nano- et microparticulaires pour l’administration de substances actives et le diagnostic, particulièrement dans le traitement des maladies inflammatoires et du cancer. Pour l’étude de l’efficacité de ces systèmes, elle a développé de nombreux modèles biologiques et pharmacologiques. L’objectif de ces dernières années a été de concevoir des systèmes microparticulaires capables de s’immobiliser au niveau du site d’action (poumons, oreille interne, artères), de concevoir des nanomédicaments fonctionnalisés capables après administration intraveineuse de cibler des cellules immunitaires ou des cellules cancéreuses (par la fonctionnalisation par des aptamères ou des polysaccharides), de concevoir des nanomédicaments pour la délivrance d’acides nucléiques codants (ARNm) et non codants (antimiR, ARNi) et enfin de développer des systèmes nanoparticulaires pour l’imagerie et la photoaccoustique. Les résultats les plus récents sont les suivants :

(i) La fonctionnalisation de liposomes par des aptamères (antiCD44 et antinucléoline) permet d’augmenter la l’accumulation tumorale ainsi que l’activité d’ARN interférents ou d’inhibiteurs d’HSP90.
(ii) Des émulsions de Pickering lipiodolées stabilisées par des nanoparticules de poly(lactide-co-glycolide) contenant de l’oxiplatine induisent une efficacité élevée dans le traitement de l’hépatocarcinome par chimioembolisation.
(iii) Le développement d’un nouveau procédé d’obtention de nanoparticules de palmitate de dexaméthasone induit une meilleure efficacité dans la réduction des symptômes inflammatoires dans un modèle murin d’arthrite rhumatoïde. L’efficacité dans le même modèle d’un antagomir anti-miR155 vectorisé par des liposomes PEGylés ou d’un ARNi anti-TNFα vectorisé par des dendrimères phosphorés cationiques a aussi pu être établie.
(iv) Le meilleur ciblage, après administration intratrachéale de liposomes recouverts d’acide hyaluronique dirigés contre des macrophages pro-inflammatoires.
(v) Le développement de systèmes hybrides (liposomes-hydrogel) pour prévenir les lésions et l’inflammation lors de l’implantation cochléaire.
(vi) La conception de nanoparticules de BODIPY à forte efficacité photoacoustique.

• Paoletti A*, Ly B, Cailleau C, Gao Fan, Péan de Ponfilly-Sotier M, Pascaud J, Rivière E, Yang L, Nwosu L, Elmesmari A, Reynaud F, Hita M, Paterson D, Reboud J, Fay F , Nocturne G, Tsapis N, McInnes I.B., Kurowska-Stolarska M, Fattal E*, Mariette X* Liposomal AntagomiR-155-5p restores anti-inflammatory macrophages and improves arthritis in pre-clinical models of Rheumatoid arthritis. Arthritis & Rhumatology, 2024, 76, 18-31.
• Ortiz-Silva N, Denis S, Vergnaud J, Hillaireau H.  Controlled hydrogel-based encapsulation of macrophages determines cell survival and functionality upon cryopreservation. Int J Pharm 2024, 650, 123491
• Yu Z, Tsapis N, Fay F, Chen L, Karpus A, Shi X, Cailleau C, García Pérez S, Huang N, Vergnaud J, Mignani S, Majoral JP, Fattal E. Amphiphilic Phosphorus Dendrons Associated with Anti-inflammatory siRNA Reduce Symptoms in Murine Collagen-Induced Arthritis. Biomacromolecules, 2023, 24, 2, 667–677.
• Bodin JB, Linger C, Gateau J, Béguin T, Lucas T, Moine L, Chapron D, Ha-Thi MH, Fatima A, Clavier G, Tsapis N, Méallet R. Fine Tuning of the Photoacoustic Generation Efficiency by Aggregation-Caused Quenching and Excitation Energy Transfer in Bodipy-Labeled Polylactide Nanoparticle. Journal of Physical Chemistry C, 2023, 127 (38): 18971-18985.
• Tessier B, Tsapis N, Fattal E*, Moine L*, Emerging nanoparticle platforms to improve the administration of glucocorticoids. Journal of Controlled Release, 2023 358, 273-292.
• Ortiz Peña N, Cherukula K, Even B, Ding-Kun J, Razafindrakoto S, Peng S, Silva A, Ménard Moyon C, Hillaireau H, Bianco A*, Fattal E *, Alloyeau D*, Gazeau F* Resolution of MoS2 nanosheets-induced pulmonary inflammation driven by nanoscale intracellular transformation and extracellular-vesicle shuttles. Advanced Materials, 2023, 35, 13, 2209615.
• Jaudoin C, Gehrke M, Grillo I, Cousin F, Ouldali M, Arteni A. A, Ferrary E, Siepmann F, Siepmann J, Simelière F, Bochot A, Agnely F. Release of liposomes from hyaluronic acid-based hybrid systems: effects of liposome size and surface. Int J Pharm. 2023 648: 123560.
• Ur Rehman M, Reynaud F, Lepetre S, Abreu S, Chaminade P, Fattal E* Tsapis N* Modulation of release and pharmacokinetics from nanoscale lipid prodrugs of dexamethasone with variable linkage chemistry. Journal of Controlled Release, 2023, 360, 293-303.
• Japiassu KB, Fay F, Marengo A, Louaguenouni Y, Cailleau C, Denis S, Chapron D, Tsapis N, Nascimento TL, Lima EM, Fattal E. Interplay between mucus mobility and alveolar macrophage targeting of surface-modified liposomes. Journal of Controlled Release, 2022, 352, 15–24.
• Mathieu C, Chamayou Q, Hyen Luong T, Naud D, Mahuteau-Betzer F, Alami M, Fattal E, Messaoudi S, Vergnaud-Gauduchon J*. Synthesis and antiproliferative activity of 6BrCaQ-TPP conjugates for targeting the mitochondrial heat shock protein TRAP1. Eur. J. Med. Chem. 2022 229, 114052.
• Bordat A, Boissenot T, Ibrahim N, Ferrere M, Levêque M, Potiron L, Denis S, Garcia-Argote S, Carvalho O, Abadie J, Cailleau C, Pieters G, Tsapis N, Nicolas J. A Polymer Prodrug Strategy to Switch from Intravenous to Subcutaneous Cancer Therapy for Irritant/Vesicant Drugs. JACS, 2022, 144(41):18844-18860.
• Bodin JB, Gateau J, Coïs J, Lucas T, Lefebvre F, Moine L, Noiray M, Cailleau C, Denis S, Clavier G, Tsapis N, Méallet-Renault R. Biocompatible and Photostable Photoacoustic Contrast Agents as Nanoparticles Based on Bodipy Scaffold and Polylactide Polymers: Synthesis, Formulation, and In Vivo Evaluation. ACS Appl Mater Interfaces, 2022, 14(36):40501-40512. doi: 10.1021/acsami.2c04874.
• Fattal, E, Fay, F, Najaudnomedicine-based delivery strategies for nucleic acid gene inhibitors in inflammatory diseases. Advanced drug delivery reviews, 2021, 175, 113809
• Canioni R, Reynaud F, Leite-Nascimento T, Gueutin C, Guiblin N, Ghermani NE, Jayat C, Daull P, Garrigue JS, Fattal E, Tsapis N. Tiny dexamethasone palmitate nanoparticles for intravitreal injection: Optimization and in vivo evaluation. Int J Pharm., 2021, 600, 120509.
• Jaudoin C, Carré F, Gehrke M, Sogaldi A, Steinmetz V, Hue N, Cailleau C, Tourrel G, Nguyen Y, Ferrary E, Agnely F, Bochot A. Transtympanic injection of a liposomal gel loaded with N-acetyl-L-cysteine: A relevant strategy to prevent damage induced by cochlear implantation in guinea pigs? Int J Pharm. 2021 604:120757.
• Costamagna F, Hillaireau H, Vergnaud-Gauduchon J, Clarisse D, Jamgotchian L., Loreau O, Denis S, Gravel E, Doris E, Fattal E. Nanotoxicology at the particle/micelle frontier: influence of core-polymerization on the intracellular distribution, cytotoxicity, and genotoxicity of polydiacetylene micelles. Nanoscale, 2020, 12, 2452-2463.
• Barillet S, Fattal E, Mura S, Tsapis N, Pallardy M, Hillaireau H, Kerdine-Römer S. Immunotoxicity of poly (lactic-co-glycolic acid) nanoparticles: influence of surface properties on dendritic cell activation. Nanotoxicology. 2019 13(5):606-62
• Binderup T, Duivenvoorden R, Fay F, et al. Imaging-assisted nanoimmunotherapy for atherosclerosis in multiple species. Science Translational Medicine 2019 11(506) eaaw7736.
• Deschamps F, Isoardo T, Denis S, Tsapis N, Tselikas L, Nicolas V, Paci A, Fattal E, de Baere T, Huang N, Moine L. Biodegradable Pickering emulsions of Lipiodol for liver trans-arterial chemo-embolization. Acta Biomater. 2019 15(87):177-186.
• Lorscheider M, Tsapis N, Ur-Rehman M, Gaudin F, Stolfa I, Abreu S, Mura S, Chaminade P, Espeli M, Fattal E. Dexamethasone palmitate nanoparticles: An efficient treatment for rheumatoid arthritis. J Control Release. 2019 28(296):179-189.
• Bordat A, Boissenot T, Nicolas J, Tsapis N. Thermoresponsive polymer nanocarriers for biomedical applications. Advanced Drug Delivery Reviews 2019 138: 167-192.
• Sauvage F, Fattal E, Al-Shaer W, Denis S, Brotin E, Denoyelle C, Blanc-Fournier C, Toussaint B, Messaoudi S, Alami M, Barratt G, Vergnaud-Gauduchon J. Antitumor activity of nanoliposomes encapsulating the novobiocin analog 6BrCaQ in a triple-negative breast cancer model in mice. Cancer Letter. 2018;432:103–111. doi:10.1016/j.canlet.2018.06.001
• Alshaer W, Hillaireau H, Fattal E. Aptamer-guided nanomedicines for anticancer drug delivery. Advanced Drug Delivery Reviews 2018 134:122-137.
• Deriu M.A, Tsapis N, Noiray M., Grasso G, El Brahmi N, Mignani S, Majoral JP, Fattal E, Danani A. Elucidating the Role of Surface Chemistry on Cationic Phosphorus Dendrimer-siRNA Complexation. Nanoscale 2018, 10(23):10952-10962.
• Alshaer W, Hillaireau H, Vergnaud J, Mura S, Deloménie C, Sauvage F, Ismail S, Fattal E. Aptamer-guided siRNA-loaded nanomedicines for systemic gene silencing in CD-44 expressing murine triple-negative breast cancer model. Journal of Controlled Release, 2018, 271:198-106.
• Picheth G, Houvenagel S, Dejean C, Couture O, Alves de Freitas R, Moine L, Tsapis N. Echogenicity enhancement by end-fluorinated polylactide perfluorohexane nanocapsules: Towards ultrasound-activable nanosystems. Acta Biomaterialia 2017, 64:313-322.
• Houvenagel S, Picheth G, Dejean C, Brûlet A, Chennevière A, Couture O, Huang N, Moine L, Tsapis N. End-chain fluorination of polyesters favors perfluorooctyl bromide encapsulation into echogenic PEGylated nanocapsules. Polymer Chemistry 2017, 78:2559-2570.
• Bohr A, Tsapis N, Andreana I, Chamarat A, Foged C, Delomenie C, Noiray M, El Brahmi N, Majoral J.P, Mignani S, Fattal E. Anti-inflammatory effect of anti-TNF-a siRNA cationic phosphorous dendrimers nanocomplexes administered intranasally in a murine acute lung injury model. Biomacromolecules 2017, 18(8):2379–2388.
• Boissenot T, Bordat A, Larrat B, Varna M, Chacun H, Paci A, Poinsignon V, Fattal E, Tsapis N. Ultrasound-induced mild hyperthermia improves the anticancer efficacy of both Taxol® and paclitaxel-loaded nanocapsules. Journal of Controlled Release 2017, 264:219-222.
• El Kechai N, Mamelle E, Nguyen Y, Huang N, Nicolas V, ChaminadeP, Yen-Nicolaÿ S, Gueutin C, Granger B, FerraryE, Agnely F, Bochot A. Hyaluronic acid liposomal gel sustains delivery of a corticoid to the inner ear. Journal of Controlled Release 2016, 226:248-257.
• Leite Nascimento T, Hillaireau H, Vergnaud J, Rivano M, Deloménie C, Courilleau D, Arpicco S, Hanes J, Fattal E. Hyaluronic acid-conjugated lipoplexes for targeted delivery of siRNA in a murine metastatic lung cancer model. International Journal of Pharmaceutics 2016, 514(1):103-111.
• Santiago L, Hillaireau H, Grabowski N, Mura S, Nascimento T, Dufort S, Coll J.L, Tsapis N, Fattal E. Compared in vivo toxicity in mice of lung delivered biodegradable and non-biodegradable nanoparticles. Nanotoxicology 2016, 10(3):292-302.
• Ruge C, Hillaireau H, Grabowski N, Beck-Broichsitter M, Cañadas O, Tsapis N, Casals C, Nicolas J, Fattal E. Pulmonary surfactant protein A – mediated enrichment of surface-decorated polymeric nanoparticles in alveolar macrophages. Molecular Pharmaceutics 2016, 13(12):4168-4178.
• Boissenot T, Fattal E, Bordat A, Houvenagel S, Valette J, Chacun H, Gueutin C, Tsapis N. Paclitaxel-Loaded PEGylated Nanocapsules of Perfluorooctyl Bromide as Theranostic Agents. European Journal of Pharmaceutics and Biopharmaceutics 2016, 108:136-144.
• Alshaer W, Hillaireau H, Vergnaud J, Ismail S, Fattal E. Functionalizing Liposomes with anti CD44 Aptamer for Selective Targeting of Cancer Cells. Bioconjugate Chemistry 2015, 26:1307-1313.
• Giacalone G, Hillaireau H, Capiau P, Chacun H, Reynaud F, Fattal E. Stabilization and cellular delivery of chitosan-polyphosphate nanoparticles by incorporation of iron. J Control Release 2014, 194:211-219
• Louguet S, Verret V, Bedouet L, Servais E, Pascale F, Wassef M, Labarre D, Laurent A, Moine L. Poly(ethylene glycol) methacrylate hydrolyzable microspheres for transient vascular embolization. Acta Biomaterialia 2014, 10:1194-205.
• Ruge C, Hillaireau H, Grabowski N, Beck-Broichsitter M, Cañadas O, Tsapis N, Casals C, Nicolas J, Fattal E. Pulmonary surfactant protein A – mediated enrichment of surface-decorated polymeric nanoparticles in alveolar macrophages. Molecular Pharmaceutics 2016, 13(12):4168-4178.
• Boissenot T, Fattal E, Bordat A, Houvenagel S, Valette J, Chacun H, Gueutin C, Tsapis N. Paclitaxel-Loaded PEGylated Nanocapsules of Perfluorooctyl Bromide as Theranostic Agents. European Journal of Pharmaceutics and Biopharmaceutics 2016, 108:136-144.
• Alshaer W, Hillaireau H, Vergnaud J, Ismail S, Fattal E. Functionalizing Liposomes with anti CD44 Aptamer for Selective Targeting of Cancer Cells. Bioconjugate Chemistry 2015, 26:1307-1313.
• Louguet S, Verret V, Bedouet L, Servais E, Pascale F, Wassef M, Labarre D, Laurent A, Moine L. Poly(ethylene glycol) methacrylate hydrolyzable microspheres for transient vascular embolization. Acta Biomaterialia 2014, 10:1194-205.

EVEN Benjamin
REYNAUD Franceline
MARENGO Alessandro
CANIONI Romain
SKANJI Rym
GIACALONE Giovana
RUGE Christian
BOHR Adam
CALLEJA GONZALES Patricia
MURA Simona

YENICE Irem
CRUZ Leticia
SANDOLO Chiara
TAETZ Sebastian
HONNAS Helge
SIMON VAZQUEZ Rosana
UR-REHMAN Mujeeb
COSCO Donato

PARCHEN Gabriela
GURCAN Serra
LEFEBVRE Flora – ingénieur d’études
GERVELAS Claudia – ingénieur d’études
ARAGAO SANTIAGO Leticia
MOUSNIER Ludivine