The team’s research focuses on the design and evaluation of innovative nanomedicines and novel materials, particularly based on polymers and lipids, for various biomedical applications such as drug delivery, tumour targeting, and the delivery of active pharmaceutical ingredients to the brain, heart, or nervous system. Another key challenge addressed by the team involves the development of nanomedicines to overcome resistance mechanisms. Their work also includes the design of multifunctional nanoparticulate systems (i.e. combining several functionalities such as imaging, therapy, targeting, etc.), the study of interactions between nanomedicines and the biological environment, and the development of three-dimensional cell culture models to investigate the fate of nanoparticles more precisely.

The team’s work has led to several major advances in the field of drug vectorisation:

•  (i) they demonstrated that coupling small molecules with anticancer, neurological, or anti-infective activity to squalene results in novel, more effective nanomedicines;
• (ii) they developed methods for functionalising polymer-based nanocarriers for drug delivery and tumour targeting;
• (iii) they established an original method for designing polymer prodrug nanoparticles that is both simple, robust, and versatile;
• (iv) they also developed an effective approach to render vinyl-based materials degradable, aiming at their use in biomedical applications;
• (v) their research contributed to understanding how surface-modified nanoparticles can cross the blood–brain barrier; and finally
• (vi) they contributed to the design, development, and characterisation of iron carboxylate and iron oxide nanoparticles for anticancer drug delivery, diagnostics, and tumour hyperthermia.

• Organic chemistry
• Polymer chemistry
• Materials chemistry
• Bioconjugation
• Physical chemistry
• Pharmacotechnics and biopharmacy
• Drug delivery
• Molecular and cell biology
• Three-dimensional cell culture
• Experimental pharmacology (animal models)
• Imaging (in vitro and in vivo)

• Tomasini L, Ferrere M, Nicolas J. Subcutaneous Drug Delivery from Nanoscale Systems. Nature Rev. Bioeng. 2024, accepted. DOI: 110.1038/s44222-024-00161-w
• Gao P, Ha-Duong T, Nicolas J. Coarse-Grained Model-Assisted Design of Polymer Prodrug Nanoparticles with Enhanced Cytotoxicity: A Combined Theoretical and Experimental Study. Angew. Chem.; Int. Ed. 2024, accepted. DOI: 10.1002/anie.202316056
• Gao P, Nicolas J, Ha-Duong T “Supramolecular Organization of Polymer Prodrug Nanoparticles Revealed by Coarse-Grained Simulations”. J. Am. Chem. Soc. 2021, 143, 17412
• Boutary S, Caillaud M, El Madani M, Vallat J-M, Loisel-Duwattez J, Rouyer A, Richard L, Gracia C, Urbinati G, Desmaële D, Echaniz-Laguna A, Adams D, Couvreur P, Schumacher M, Massaad C, Massaad-Massade L. Squalenoyl siRNA PMP22 nanoparticles, a potent therapy for Charcot-Marie-Tooth disease type 1A. Nature Commun. Biol. 2021, 4, 317
• Pautu V, Zaho H, Mielcarek A, Stella B, Balasso A, Couvreur P, Serre C, Mura S. When drug nanocarriers miss their target: extracellular diffusion and cell uptake are not enough to be effective. Biomater. Sci. 2021, 9, 5407
• Habas K, Soldevila-Barreda J J, Azmanova M, Rafols L, Pitto-Barry A, Anderson D, Barry N P E. “Evaluation of the toxicity of two electron-deficient half-sandwich complexes against human lymphocytes from healthy individuals”. ChemMedChem 2021, 16, 624-629
• Ho D-K, Murgia X, De Rossi C, Chrismann R, Hüfner de Mello Martins AG, Koch M, Andreas A, Herrmann J, Müller R, Empting M, Hartmann RW, Desmaele D, Loretz B, Couvreur P, C-M Lehr “Squalenyl Hydrogen Sulfate Nanoparticles for Simultaneous Delivery of Tobramycin and Alkylquinolone Quorum Sensing Inhibitor to Eradicate P. aeruginosa Biofilm Infections”. Angew. Chem., Int. Ed. 2020, 59, 10292
• Dormont F, Brusini R, Cailleau C, Reynaud F, Peramo A, Gendron A, Mougin J, Gaudin F, Varna M, Couvreur P “Squalene-based multidrug nanoparticles for improved mitigation of uncontrolled inflammation” Science Adv. 2020, 6, eaaz5466
• Mougin J, Yesylevskyy S0, Bourgaux C, Chapron D, Michel JP, Dosio F, Stella B, Ramseyer C, Couvreur P “Stacking as a Key Property for Creating Nanoparticles with Tunable Shape: The Case of Squalenoyl-Doxorubicin”. ACS Nano 2019, 13, 12870
• Feng J, Lepetre-Mouelhi S, Gautier A, Mura S, Cailleau C, Coudore F, Hamon M, Couvreur P “A new painkiller nanomedicine to bypass the blood-brain barrier and the use of morphine”. Science Advances 2019, 5, eaau5148
• Peramo A., Dumas A. , Remita H., Benoît M., Yen-Nicolay S., Corre R., Louzada R. A., Dupuy, C., Pecnard S., Lambert B., Young Y., Desmaële D., Couvreur P. “Selective modification of a native protein in a patient tissue homogenate using palladium nanoparticles”. Chem. Commun. 2019, 55, 15121
• Guégain E, Tran J, Deguettes Q, Nicolas J. “Degradable Polymer Prodrugs with Adjustable Activity from Drug-Initiated Radical Ring-Opening Copolymerization”. Chem. Sci. 2018, DOI: 10.1039/c8sc02256a
• Lazzari G, Nicolas V, Matsusaki M, Akashi M, Couvreur P, Mura S. “Multicellular spheroid based on a triple co-culture: A novel 3D model to mimic pancreatic tumor complexity.” Acta Biomate. 2018, 78, 296
• Vinciguerra D, Denis S, Mougin J, Jacobs M, Guillaneuf Y, Mura S, Couvreur P, Nicolas J. “A Facile Route to Heterotelechelic Polymer Prodrug Nanoparticles for Imaging, Drug Delivery and Combination Therapy”. J. Control. Release 2018, DOI: 10.1016/j.jconrel.2018.08.013
• Sobot D, Mura S, Rouquette M, Vulosavljevic B, Cayre F, Buchy E, Pieters G, Garcia Argote S, Windbergs M, Desmaële D, Couvreur P. “Conjugation of squalene to gemcitabine as unique approach exploitins endogenous lipoproteins for drug delivery”. Mol. Ther. 2017, 25, 1596
• Tardy A, Honoré JC, Tran J, Siri D, Delplace V, Bataille I, Letourneur D, Perrier J, Nicoletti S, Maresca M, Lefay C, Gigmes D, Nicolas J, Guillaneuf Y. “Radical Copolymerization of Vinyl Ethers and Cyclic Ketene Acetals as a Versatile Platform to Design Functional Polyesters.” Angew. Chem., Int. Ed. 2017, 56, 16515.
• Kotelevets L, Chastre E, Caron J, Mougin J, Bastian G, Pineau A, Walker F, Lehy T, Desmaële D, Couvreur P. “A squalene-based nanomedicine for oral treatment of colon cancer”. Cancer Res. 2017, 77, 2964
• Sobot D, Mura S, Yesylevskyy SO, Dalbin I, Cayre F, Bort G, Mougin J, Desmaële D, Lepetre Mouelhi S, Pieters G, Andreiuk B, Klymchenfo AS, Paul JL, Ramseyer C, Couvreur P. “Conjugation of squalene to gemcitabine as unique approach exploiting endogenous lipoproteins for drug delivery”. Nature Commun. 2017, 8, 15678
• Simon-Yarza T, Gimenez-Marques M, Mrimi R, Mielcarek A, Gref A, Horcajada P, Serre C, Couvreur P. “Smart metal-organic-framework nanomaterial for lung targeting”. Angew. Chem., Int. Ed. 2017, 56, 15565
• Bao Y, Boissenot T, Guégain E, Desmaële D, Mura S, Couvreur P, Nicolas J. “Simple Synthesis of Cladribine-Based Anticancer Polymer Prodrug Nanoparticles with Tuneable Drug Delivery Properties”. Chem. Mater. 2016, 28, 6266
• Delplace V, Nicolas J “Degradable Vinyl Polymers for Biomedical Applications” Nature Chem. 2015, 7, 771
• Romero-Canelón I, Phoenix B, Pitto-Barry A, Tran J, Soldevila-Barreda J J, Kirby N, Green S, Sadler P J, Barry N P E. “Arene ruthenium dithiolato–carborane complexes for boron neutron capture therapy (BNCT)”. J. Organomet. Chem. 2015, 796, 17-25.
• Barry N P E, Pitto-Barry A, Romero-Canelón I, Tran J, Soldevila-Barreda J J, Hands-Portman I, Smith C J, Kirby N, Dove A P, O’Reilly R K, Sadler P J. “Precious metal carborane polymer nanoparticles: characterisation of micellar formulations and anticancer activity”. Faraday Discussions, 2015, 175, 229-240.
• Pitto-Barry A, Barry N P E, Russo V, Heinrich B, Donnio B, Therrien B, Deschenaux R. “Designing supramolecular liquid-crystalline hybrids from pyrenyl-containing dendrimers and arene ruthenium metallacycles”. J. Am. Chem. Soc. 2014, 136, 50, 17616–17625
• Maksimenko A, Dosio F, Mougin J, Ferrero A, Wack S, Harivardhan Reddy L, Weyn A, Lepeltier E, Bourgaux C, Stella B, Cattel L, Couvreur P. “Squalenoylated Doxorubicin: A New Long Circulating and Non Pegylated Anticancer Nanomedicine”. Proceeding Nat. Acad. Sci., USA 2014 111, E217
• Mackiewicz, N, Nicolas, J, Hanke N, Noiray M, Mougin J, Daveu C, Lakkireddy Reddy L, Bazile D, Couvreur P. “Precise engineering of multifunctional PEGylated polyester nanoparticles for cancer cell targeting and imaging”. Chem. Mater. 2014, 26, 1834
• Maksimenko A, Alami M, Zouhiri F, Brion JD, Pruvost A, Mougin J, Hamze A, Boissenot T, Provot O, Desmaële D, Couvreur P. “Therapeutic modalities of squalenoyl nanocomposites in colon cancer: an ongoing search for improved efficacy”. ACS Nano 2014, 8, 2018
• Gaudin A, Yemisci M, Eroglu H, Lepêtre-Mouelhi S, Turkoglu OF, Donmez-Demir B, Caban S, Sargon MF, Garcia-Argote S, Pieters G, Loreau O, Rousseau B, Tagit O, Hildebrandt N, Le Dantec Y, Mougin J, Valetti S, Chacun H, Nicolas V, Desmaële D, Andrieux K, Capan Y, Dalkara T, Couvreur P. “Squalenoyl Adenosine Nanoparticles provide Neuroprotection after Stroke and Spinal Cord Injury”. Nature Nano. 2014, 9, 1054
• Mura S, Nicolas J, Couvreur P. “Stimuli-responsive nanocarriers for drug delivery”. Nature Materials 2013, 12, 991-1003.
• Harrisson S, Nicolas J, Maksimenko A, Duc Trung B, Mougin J, Couvreur P. “Nanoparticles with In Vivo Anticancer Activity from Polymer Prodrug Amphiphiles Prepared by Living Radical Polymerization”. Angew. Chem., Int. Ed. 2013, 52, 1678
• Le Droumaguet B, Nicolas J, Brambilla D, Mura S, Maksimenko A, Salvati E, De Kimpe L, Zona C, Airoldi C, Canovi M, Gobbi M, Noiray M, La Ferla B, Nicotra F, Scheper W, Flores O, Masserini M, Andrieux K, Couvreur P. « Versatile and Efficient Targeting Using a Single Nanoparticulate Platform: Application to Cancer and Alzheimer’s Disease » ACS Nano 2012, 6, 5866-5879.

• Ecole doctorale ITFA : Innovation Thérapeutique : du Fondamental à l’Appliqué (ED569)
• M2 Pharmacotechnie et Biopharmacie (lien de la formation et lien institutionnel)

PASSANNANTE Rossana – research scientist, EMBL Barcelona
LE Dao – research scientist, SNF
MARTINEZ Alvaro – Assistant Prof, Complutense Univ of Madrid
BOSSION Amaury – research scientist, Huntsman
BERNARDI Sarah
GISBERT GARZARAN Miguel
BIDAN Nadège
UGRINIC Martina
PAUTU Vincent
GAUTIER Anne
BALASSO Anna
ABED Nadia
BORT Guillaume
CHAPUIS Hubert
SAID-HASSANE Fatouma
DAOUD-MAHAMMED Samia
SLIWINSKI Eric
DUMAS Anaëlle
BAO Yinyin
BLIN Thomas
MAKKY Nada – research scientist, Imescia
GENEVAZ Nicolas – project manager, Calidris
GOPALAKRISHNAN Gopakumar –
BECK-BROICHSITTER Moritz
HANDKE Nadège – head of formulation, LFB
SALEM Wafa
HARRISSON Simon – CNRS Researcher, Univ Bordeaux
MACKIEWICZ Nicolas – pilot plant manager, Bracco
LE DROUMAGUET Benjamin – Associate Prof, Univ Paris-Est
Violeta Rodriguez
CHIPER Manuela
MACKSIMENKO Andrey
KOTELEVETS Larissa

GUERASSIMOFF Léa – postdoc, Univ Ghent
GENDRON Amandine
DA SILVA Alexandre
GAO Ping – postdoc, Zhejiang Univ of Technology
TOMASINI Lorenzo – research scientist, Sanofi
JAKPOU Justine – research scientist, Ziphius Vaccines
PESENTI Théo – postdoc, UCLA
LAGES Maëlle – research scientist, Veto-pharma
ZHU Chen (Justin) – postdoc, Univ Strasbourg
COPPENS Eléonore
FERRERE Marianne – research scientist, Ipsen
DORMONT Flavio
BRUSINI Romain
PERAMO Arnaud
BUCHI Eric
TRAN Johanna – research scientist, Stilla Technologies
VINCIGUERRA Daniele
FENG Jiao
ROUQUETTE Marie (avec équipe 5)
BORDAT Alexandre – CTO, Imescia
GUEGAIN Elise – Research scientist, Medicen
SOBOT Dunja
DELPLACE Vianney – INSERM researcher, Univ Nantes
GAUDIN Alice
BUI Duc Trung
BRAMBILLA Davide – Assistant Prof, Univ Montreal
PILLONI Martina
BILDSTEIN Lucien
SEMIRAMOTH Nicolas
VALETTI Sabrina
AGOSTONI Valentina
RODRIGUEZ Violeta
RALAY-RANAIVO Bettina
CARON Joachim
RAOUANE Mouna
CHALATI Tamim
OTHMAN Mohammad
LALANNE Muriel

THIERCELLIN Julie – Product Development & Supply Chain Manager, CUT BY FRED
NGUYEN Khanh – PhD student, Dartmouth Univ
DEHISSI Samy
QUINTANA ROMERO Dulce Alitzel
BAUSEROY Hannah
LUMBA Joseph
TO Thu Ba, PhD student – Univ Paris-Saclay
GUERASSIMOFF Léa – Postdoc, Univ Ghent
ISHII Seika – PhD student, University of Bielefeld
DOMINGO LOPEZ Daniel – PhD student, National University of Ireland
FERRERE Marianne – Research scientist, Ipsen
PESENTI Théo – Postdoc, UCLA
LEVEQUE Manon – PhD student, Univ Bordeaux
CRESSONNIER Jonathan – Expert assurance qualité, CRTL
SOLIMAN Nancy – R&D scientist, Calyxia
DEGUETTES Quentin – R&D scientist, Pensatech Pharma
BEN CHRAIT Imen – Head of polymer platform, Chryso
TRAN Johanna – Research scientist, Stilla Technologies
EL-ASMAR Arlette – Clinical Researcher, IFM
GUEGAIN Elise – Research scientist, Medicen
KORCHIA Laetitia – Consultant, Ayming
SANA Allaoua – Site director, FLASHLAB SAS
GRIVES Sophie – Project Manager, Medesis Pharma
CHENAL Marion – Project manager, Saint-Gobain
ROISIN Juliette – Quality manager, Lallemand
BENSAID Fethi – Head of formulation, Sanofi
PIERSON Laure-Anne – Associée-Directrice, Nature-Zen

MARTIN-GUINEBERT Cloé – Healthcare Industry Engineer, VIQI