Nanomedicine for the treatment of severe diseases

Our research is focused on the development and the evaluation of innovative nanomedicines and new materials, particularly based on polymers or lipids, for a broad range of different biomedical applications, such as drug delivery, cancer tissue/cell targeting and the delivery to the brain or to the heart. The design of new nanomedicines to overcome resistance mechanisms is also another important task of our group, together with the design of multifunctional nanoparticulate systems (ie, combining several functionalities: imaging, therapy, targeting, etc.), the evaluation of the interactions of nanoparticles with the biological media and the development of 3D cell culture models to better investigate the fate of nanoparticles.

Several key achievements in the field of drug delivery recently derived from our research such as:

• (i) the coupling of squalene to small drugs with anticancer, neurological or anti-infective activities leading to new and more efficient nanomedicines;
• (ii) the development of multifunctional polymer nanoparticles for cancer cell targeting;
• (iii) the discovery of an original, simple and flexible approach to prepare polymer prodrugs nanocarriers;
• (iv) a robust method to prepare a broad range of different degradable vinyl polymers for biomedical applications;
• (v) the preparation of polymer nanoparticles with BBB crossing ability, and
• (vi) the co-development, the characterization and the evaluation of iron oxide and iron carboxylate nanoparticles for the delivery of anticancer drugs, for diagnostic purposes and for hyperthermia.

• Organic synthesis
• Polymer chemistry
• Materials chemistry
• Bioconjugation
• Physico-chemistry
• Pharmaceutical technology and drug delivery
• Cellular and molecular biology
• 3D cell culture models
• Pharmacology (animal experiments)
• In vitro/in vivo imaging

PESENTI Théo - PhD student
LAGES Maëlle - PhD student
ZHU Chen (Justin) - PhD student
Alvaro MARTINEZ - Post-doctoral Researcher
COPPENS Eléonore - PhD student
BOSSION Amaury - PhD student
UGRINIC Martina - Post-doctoral Researcher
FERRERE Marianne - PhD student
DORMONT Flavio - PhD student
BRUSINI Romain - PhD student
PERAMO Arnaud - PhD student
BUCHI Eric
TRAN Johanna - PhD student
VINCIGUERRA Daniele
FENG Jiao
ROUQUETTE Marie (avec équipe 5)
BORDAT Alexandre
GAUTIER Anne
BORT Guillaume
GUEGAIN Elise - PhD student
SOBOT Dunja
DELPLACE Vianney
GAUDIN Alice
DUMAS Anaëlle
BAO Yinyin - Post-doctoral Researcher
BLIN Thomas
MAKKY Nada
GENEVAZ Nicolas
GOPALAKRISHNAN Gopakumar
BECK-BROICHSITTER Moritz
SALEM Wafa
HANDKE Nadège - PhD student
HARRISSON Simon - Post-doctoral Researcher
MACKIEWICZ Nicolas
LE DROUMAGUET Benjamin
BUI Duc Trung
BRAMBILLA Davide
PILLONI Martina
BILDSTEIN Lucien
VALETTI Sabrina
AGOSTONI Valentina
RODRIGUEZ Violeta
CHIPER Manuela
MACKSIMENKO Andrey
KOTELEVETS Larissa
RALAY-RANAIVO Bettina
CARON Joachim
RAOUANE Mouna
CHALATI Tamim
OTHMAN Mohammad
LALANNE Muriel

• ITFA : Innovation Thérapeutique : du Fondamental à l’Appliqué

Publications majeures

• 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.

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