Community Research and Development Information Service - CORDIS


The world-wide spread of antibiotic-resistant microorganisms can be viewed as an ecological consequence of the systematic use of antimicrobial agents. Resistant bacteria prevail in healthcare environments where antibiotic selective pressure is intensive. Nanocarriers based on cyclodextrins (CDs) are particularly appealing for the delivery of antibiotics, an approach of main interest for tuberculosis (TB), infections related to Salmonella typhimurium (ST) , Staphyloccocus aureus (SA) and for species most frequently implicated in hospital infections such as enteric gram-negative rods. The CycloN Hit project takes advantage of the high level inter­disciplinary expertise of the partners to efficiently encapsulate and protect antibiotics in CD-based nanocarriers to combat resistant bacteria (attachment: Nanocarriers_CyclonHit).
This will be accomplished through research training of 11 Early Stage and 5 Experienced Researchers who will gather expertise of 11 Full and 6 Associated partners. The final goal is to bring to the preclinical studies an antibiotic formulation for the treatment of TB and more tailored alternative therapeutic approaches for other resistant microorganisms.
Bacteria continuously mutate acquiring resistance genes and so, increased research efforts will be needed over the years to keep on discovering novel adapted treatments. In this context, the next generation of highly educated researchers and industrials need to be trained to deal with the complex issues related to increasing antibiotic resistance. The CycloN Hit project aims that young scientists receive a well-planned personalized training in an interdisciplinary domain going from chemistry to nanotechnology, microbiology and in vivo efficacy studies. These scientists should acquire fundamental knowledge to possess the “common language” to work efficiently at the interface between different domains. Then, they need receiving state of the art information, best suited research methods and technology in the proposed field, as well as numerous opportunities to contact and blend with the private sector (SMEs) to gain a “real-world” view. Besides, the young scientists need communication skills, as first-class science needs transfer to the large public and good diffusion in the international community. High level ERSs and ERs have been employed and been offered the opportunity to develop their research planning, report and present their work in very competitive both academic and private sectors.
In the first two years of the project, several main scientific achievements were obtained. Engineered multifunctional nanocarriers could efficiently encapsulate a powerful synergic anti-TB drug combination discovered by Pasteur Institute, Cyclon Hit partner. In a complementary approach, cationic CDs able to target bacterial cell walls were successfully synthesized. These novel derivatives are well adapted to form inclusion complexes with antibiotics. We synthesized a series of CD derivatives bearing targeting ligands to functionalize the surface of nanoparticles in order to increase their interaction with infected cells. Interestingly, a novel polymeric derivative discovered in the consortium has been used to synthesize core-shell silver and silver-gold nanoparticles of high interest for their antibacterial action. For the first time, a robotic platform has been used for high-throughput in vitro screening of the CD-based nanoplatforms on infected cells. In vivo studies showed the superiority of CD-based nanocarriers over conventional nanoparticles in reducing the bacterial loads in the lungs in a model of TB-infected mice.
Expected results and potential impact:
The introduction of nanotechnology in pharmacology (“nanomedicine”) has revolutionized the delivery of drugs, opening the way towards new treatments with improved efficacies and specificities. In this sense, the use of engineered CD-based antibiotic nanocarriers in Cyclon Hit is a promising strategy. Thus, Cyclon Hit will propose novel therapeutic approaches to deliver the well-documented existing drugs in an optimized fashion to: i) protect the drugs toward degradation; ii) increase antibiotic bioavailability; iii) reduce drug toxic side effects; iv) increase patient compliance to the treatment and iv) reduce treatment duration and related costs. The nanoparticles with best results in vitro will be tested in vivo and the formulations will be scaled up (attachment: Cyclon Hit logo).

Contact details: Dr Ruxandra Gref, CNRS, Université Paris Sud, Orsay,

Major Journal Publications:
1. “A “green” strategy to construct non-covalent, stable and bioactive coatings on porous MOF nanoparticles”, V. Agostoni, P. Horcajada, M. Noiray, M. Malanga, A. Aykaç, L. Jicsinszky, A. Vargas-Berenguel, N. Semiramoth, S. Daoud-Mahammed, V. Nicolas, C. Martineau, F. Taulelle, J. Vigneron, A. Etcheberry, C. Serre, R. Gref, Scientific Reports 2015, 5:7925, DOI:10.1038/srep07925.
2. “Fighting against bacterial resistance to penicillins with CDs”, E. Fenyvesi, Cyclodextrin News 2014, 285(11), 1-7
3. “A multicomponent gel for nitric oxide photorelease with fluorescent reporting”, A. Fraix, N. Kandoth, R. Gref, and S. Sortino, Asian J. Org. Chem. 2015, 4(3), 256-261, DOI: 10.1002/ajoc.201402267
4. “Cyclodextrins, blood-brain barrier, and treatment of neurological diseases”, M. Vecsernyés, F. Fenyvesi, I. Bácskay, M.A. Deli, L. Szente, E. Fenyvesi, Archives of Medical Research 2014, 45, 711-729, DOI:
5. “Cyclodextrins in the Battle against Antibiotic Resistant Microorganisms: Mimicking Cyclic Peptide Antibiotics”, G. Benkovics, Cyclodextrin News 2015, 29(3), 1-7
6. “Anionic cyclodextrins as versatile hosts for pharmaceutical nanotechnology: Synthesis, drug delivery, enantioselectivity, contrast agents for MRI”, I. M. Mavridis, K. Yannakopoulou, Int. J. Pharm. 2015, 492, 275-290. doi:10.1016/j.ijpharm.2015.06.004. Mini-review
7. “Synthesis, characterization and photo-bactericidal activity of silanized xanthene-modified bacterial cellulose membranes”, H. Hettegger, M. Gorfer, S. Sortino, A. Fraix, D. Bandian, C. Rohrer, W. Harreither, A. Potthast, T. Rosenau, Cellulose, Published online Sept 4, 2015. DOI 10.1007/s10570-015-0715-y
8. “Efficient “green” encapsulation of a highly hydrophilic anticancer drug in Metal-organic frameworks nanoparticles”, V. Rodriguez-Ruiza, A. Maksimenko, R. Anand, S. Monti, V. Agostoni, P. Couvreur, M. Lampropoulou, K. Yannakopoulou, R. Gref, J. Drug Targeting, 2015, 23(7-8), 759-767. DOI:10.3109/1061186X.2015.1073294. Invited article in special issue honouring Pr. R. Langer.
9. “Towards an optimized treatment of intracellular bacteria infections: input of nanoparticulate drug delivery systems”, C. Ladavière, R. Gref, Nanomedicine, Invited review article. DOI:10.2217/nnm.15.128
10. “Polystyrene nanofiber materials for visible light-driven dual antibacterial action via simultaneous photogeneration of NO and 1O2”, J. Dolanský, P. Henke, P. Kubát, A. Fraix, S. Sortino and J. Mosinger, ACS Mater. Interf. Sci. DOI: 10.1021/acsami.5b06233
11. “Multilamellar Nanoparticles Self-Assembled from Opposite Charged Blends: Insights from Mesoscopic Simulation”, S. Nie, X. Zhang, R. Gref, P. Couvreur, Y. Qian, L. Zhang, J. Phys. Chem. 2015, 119, 20649−20661. DOI: 10.1021/acs.jpcc.5b03833
12. “Effect of cyclodextrins on the degradation rate of benzylpenicillin”, A.Popielec, E. Fenyvesi, K. Yannakopoulou and T. Loftsson, Die PHARMAZIE, 2016, 71, 68–75. DOI: 10.1691/ph.2016.5114
13. “New synthetic strategies for xanthene-dye-appended cyclodextrins”; M. Malanga, A. Darcsi, M. Balint, G. Benkovics, T. Sohajda, S. Beni; Beilstein Journal of Organic Chemistry 2016, 12, 537-548. DOI: 10.3762/bjoc.12.53
14. Artemisinin, the Nobel Prize Winner Drug in Cyclodextrin-Enabled Formulations
E. Fenyvesi, G. Benkovics, Cyclodextrin News 2016, 30(3), 1-6
15. A. Fraix, N. Marino and S. Sortino, Phototherapeutic Release of Nitric Oxide with Engineered Nanoconstructs, Topics in Curr. Chem. 2016, 370, 225-257. Springer In “Light-responsive nanostructured systems for applications in nanomedicine”, S. Sortino, a guest editor

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