Typologie d'actualités: Team Cell Biology, Molecular Targets and Innovative Therapies

A new luminescence for the direct follow-up of drug delivery

Liposomes are nanocapsules widely used for the in vivo transport and delivery of therapeutic or diagnostic agents, or both. The therapeutic agent will only become active upon its release, thus sparing healthy tissues. The follow up of such release process is crucial to understand and control the drug action.

The previously reported approaches are based on optical imaging, using exclusively organic fluorophores or inorganic nanoparticles, co-encapsulated with the drug in the liposome.

The use of luminescent lanthanide complexes is an alternative which offers a number of advantages, including the capacity of those complexes to emit in the near infrared (NIR) region, enabling their detection in biological media.

The CBM research teams have developed an original nanocapsule : a liposome comprising an Ytterbium complex encapsulated with doxorubicin (anticancer agent). The NIR emission of the lanthanide complex is only observed when the drug is encapsulated. This NIR luminescence signal can therefore enable the direct follow-up, and in real time, of the integrity of the liposome, and can thus be used to detect the drug release.

An in vivo proof of concept was performed and the lanthanide luminescent signal could be detected in a mouse model of breast cancer.

Références de l'article :

Doxorubicin-sensitized Luminescence of NIR-emitting Ytterbium Liposomes: Towards Direct Monitoring of Drug Release,

Sara Lacerda, Anthony Delalande, Svetlana V. Eliseeva, Agnès Pallier, Célia S. Bonnet, Frédéric Szeremeta, Sandra Même, Chantal Pichon, Stéphane Petoud, Eva Toth

Angewandte Chemie Int. Ed. 13 août 2021  https://doi.org/10.1002/anie.202109408

 

See the news on CNRS Chemistry Institute site

 

 




Biotechnocentre 33rd conference

The 33rd Biotechnocentre conference will be held on October 7 and 8, 2021  at Center Parcs Domaine Les Hauts de Bruyères - Rue Lamotte - 41 600 Chaumont-sur-Tharonne.

With the participation of Doctoral School 549 "Santé, Sciences Biologiques et Chimie du Vivant" (SSBCV).

Among the speakers announced, Vincent Aucagne, head of the thematic group "Synthetic proteins and bioorthogonal chemistry" " will give a conference entitled "Methodological developments for the chemical synthesis of proteins"

Registration before September 3, 2021 at biotechnocentre@sfr.fr

See the poster

Conferences program

SFNano Webinar – March 31st, 2021

Free Webinar "mRNA Lipid Nanoparticle formulations for mRNA-vaccines"

March 31st, 2021 3:30 – 6:00 pm (Paris Time Zone / CET)

MRNA vaccines have experienced an unprecedented burst  in basic and clinical research. These vaccines were among the first available vaccines to fight the Covid-19 pandemic and they demonstrated the potency and versatility of mRNA technology to protect against infectious disease. As this new delivery technology is going to be applied to hundreds of millions of people in the European Community and around the world, this webinar will present the key features of lipid nanoparticles (LNPs) used for the COVID-19 mRNA vaccine and will draw first lessons learned for further vaccine development and beyond for new mRNA therapies. Find out more.

Online registration

 




Targeting the LINGO-1 receptor and its hetero-complexes: new therapeutic perspectives for the treatment of demyelinating and neurodegenerative diseases

LINGO-1 is a transmembrane protein mainly expressed in neurons and oligodendrocytes where it negatively regulates regeneration, neuronal survival, oligodendrocyte differentiation and myelination. Its expression was shown to be dysregulated in several brain disorders, in particular, Parkinson's disease and multiple sclerosis, which makes LINGO-1 a particular interesting therapeutic target. Three homologs LINGO-2, LINGO-3 and LINGO-4 have been described in human but until now their functions remain largely unknown. In this article published in the FASEB Journal, the researchers evaluated the expression, the cerebral distribution and the colocalization of these different homologs in several brain areas. They also showed the formation of hetero-complexes of LINGO-1 with its homologs in the brain, revealing a new level of complexity in the regulation of the activity of these receptors. The demonstration of this LINGO-1 signaling opens the way to new strategies to modulate its activity for the treatment of brain disorders.

Guillemain, A., Y. Laouarem, L. Cobret, D. Stefok, W. Chen, S. Boch, A. Zahaf, L. Blot, F. Reverchon, T. Normand, M. Decoville, C. Grillon, E. Traiffort and S. Morisset (2020). "LINGO family receptors are differentially expressed in mouse brain and forms native multimeric complexes " FASEB J (2020) doi : 10.1096/fj.202000826R

Creation of a predictive model of metabolic changes characteristic of neurodegenerative diseases

Drosophila flies are versatile animal models for the study of genetic mutations in neuronal pathologies. Their small size allows performing in vivo experiments to obtain high resolution nuclear magnetic resonance spectra. Dr. Martine Decoville of CBM, researchers from CEMHTIand ESPCI Paris used spatially-resolved ¹H high-resolution MAS NMR to investigate in vivo metabolite contents in different segments of the fly body. A comparative study of metabolic changes was performed for three neurodegenerative disorders: two cell-specific neuronal and glial models of Huntington disease and a model of glutamate excitotoxicity. These 3 pathologies are characterized by specific and sometimes anatomically localized variations in metabolite concentrations. In two cases, the modifications of ¹H MAS NMR spectra localized in fly heads were significant enough to allow the creation of a predictive model.

Spatially-resolved metabolic profiling of living Drosophila in neurodegenerative conditions using 1H magic angle spinning NMR - Scientific Reports (2020) https://doi.org/10.1038/s41598-020-66218-z

Disturbed expression of autophagy genes in blood of Parkinson’s disease patients

Parkinson's disease is a neurodegenerative pathology characterized by the presence of protein aggregates in the neurons of patients. This neurotoxic accumulation of misfolded proteins could be due to insufficient elimination by autophagic cellular mechanisms. Alain Legrand's group has just published a study highlighting an alteration in the expression of genes coding for autophagy proteins in the blood of patients with Parkinson's disease. This pilot study, carried out in collaboration with the Neurology Department of the Centre Hospitalier Régional d'Orléans (CHRO) and the Fundamental Informatics Laboratory of the University of Orléans (LIFO), shows that defects in autophagic systems that affect the brain of patients can also be detected in peripheral blood cells. These deregulated genes could thus constitute diagnostic markers of Parkinson's disease that can be measured non-invasively after a simple blood test.

El Haddad S. et al, Disturbed expression of autophagy genes in blood of Parkinson's disease patients.  Gene vol. 738 (2020): 144454

Claudine Kieda, Research Director Emeritus at the CBM, honored at the “Outstanding Poles in France” gala.

 

This action by the Polish Polskie Godlo Promocyjne Teraz Polska Foundation is awarded to Polish and Polish people permanently residing in France who have achieved great success in their work, who are recognized in their communities for initiatives and activities to promote a positive image of Poland and the Poles.

The aim is to make these people better known in France and also in Poland, where they often remain anonymous.

The title "Outstanding Polish" can be awarded in the following five categories: Business, Culture, Research / Science, Personality and "Young Poles".