Microsoft word - nanofol_publishable summary_m12_280111.doc
Folate-based nanobiodevices for integrated diagnosis/therapy targeting chronic inflammatory diseases 1.1. Context and project objectives
It is estimated that inflammatory diseases affect more than 80 million people worldwide leading to untold suffering, economic loss and premature death. Considering life expectancy in Europe, these numbers are expected to increase in the next 20 years. Moreover, studies have shown that disorders such as rheumatoid arthritis (RA) can shorten life span by 10 years. The treatment of chronic inflammatory disorders, including RA, remains a chal enge for the medical and scientific community. The emergence of new drugs creates new options though it also entails high costs, complicated drug administration, allergic reactions and potential y fatal side effects. Therefore more efficient strategies have to be identified in order to improve inflammatory disease treatment while decreasing the side effects with an improved cost-benefit ratio. Nano-enabled drug delivery systems will take therapy of chronic inflammatory disorders to a new level by creating a new, highly specific and efficient strategy, with reduced treatment costs.
The NANOFOL project has adopted a specific risk amelioration strategy to attain objectives in a step-by-step approach in order to gradual y improve the concept (specificity, stability, side effects and efficacy) from lower to higher risk solutions ensuring reduced animal testing and high human safety.
NANOFOL wil improve treatment of chronic inflammatory diseases by fulfil ing the fol owingobjectives:
Design, development and production of nanobiodevices directly targeting effector
Experimental design that will enable minimal animal experimentation.
Development of a strategy to assess potential life cycle risks ensuring safe
Setting-up better citizen awareness on nanomedicine-based therapies and training
1.2. Status at M12
NANOFOL has acomplished until now the overal objectives established in the initial plan. The consortium discussed and defined several possibilities for the global nanodevicestrategy, in order to reach delivery technology products with therapeutic potential. In this firstyear the optimal conditions were established for the production of Folate BasedNanobiodevice (FBN) prototypes, incorporating components (such as folate-surfactant neckdomain peptides) intended to provide both target specificity and improved stability. Ourresults suggest that these FBN, liposomal or protein-based nanoparticles can encapsulatedrugs such as celecoxib. These FBN have been tested for internalization in FRα- and FRα+ cel s and sugest target cel specificity. The consortium wil continue to promote optimizationof production methodologies, such as the proposed development of microreactor systemswhich would al ow the scale-up of liposome production. Several in vitro models for testingspecific cel uptake of nanodevices, as wel as the molecular and biochemical effects ofexposure to such particles, have been established. We were able of identifying candidategenes for downregulation in activated macrophages by RNA interference. Special attention isbeing given to minimizing the use of animal testing by establishing other models. It hasbecome evident that the macrophage differentiation scheme (M1 versus M2 macrophages),in particular in humans, must be further clarified. This wil contribute not only improved basicscientific knowledge of rheumatoid arthritis (RA) but also to valid protocols for testingactivated macrophage-targeting therapies. The first anti-FRβ monoclonal antibodies have been produced and the quest for relevant macrophage-associated target antigens for theantibody-based bispecific nanobiodevice is underway. NANOFOL nanobiodevices targetingactivated macrophages may become an interesting theranostics solution, i.e. simultaneoustreatment and diagnosis site of inflammation in RA patients. The production of a validated,stable, specific FBN with incorporated imaging agent and therapeutic agent (drugs orsiRNAs) by the NANOFOL consortium wil have immediate application in al inflammatorydiseases where activated macrophages contribute to the disease process. Consortium Coordinator Pr. Artur CAVACO-PAULO, [email protected] Universidade do Minho – Portugal www.nanofol.eu
Technische Universitaet Graz – Austria
Nederlandse Organisatie Voor Toegepast Natuurwetenschappelijk Onderzoek –
Instituto de Biologia Molecular e Celular – Portugal
Institut National de la Santé et de la Recherche Médicale – France
Medizinische Universitaet Wien – Austria
“Aurel Vlaicu” University of Arad – Romania
Institut National de l’Environnement et des risques – France
ALFAMA – Investigacao e Desenvolvimento de Produtos Farmaceuticos, Lda –
The research leading to these results has received funding from the European Union
Seventh Framework Programme (FP7/2007-2013) under grant agreement n° NMP4-LA-2009-228827 NANOFOL.
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