Description du projet
Des nanosondes fluorescentes pour la biodétection amplifiée
Des scientifiques étudient les fonctions cellulaires en analysant la manière dont interagissent les divers composants, y compris les biomolécules et les multiples organites. Traditionnellement, il s’agit de suivre et de visualiser des biomolécules individuelles dans des cellules vivantes à l’aide de sondes fluorescentes. Toutefois, la luminosité limitée des sondes fluorescentes existantes entrave la détection moléculaire, ce qui pose des problèmes techniques. Financé par le Conseil européen de la recherche, le projet BrightSens entend développer des nanoparticules organiques fluorescentes ultra-lumineuses capables de convertir un seul événement de reconnaissance moléculaire en une réponse optique de centaines de colorants encapsulés. Un concept d’amplification du signal basé sur des nanoparticules fluorescentes est donc proposé pour accroître la sensibilité de la biodétection. Ces nanoparticules présentent un immense potentiel pour la détection des récepteurs membranaires et de l’ARN intracellulaire dans les cellules cancéreuses, ouvrant ainsi de nouvelles perspectives en recherche biomédicale.
Objectif
Existing fluorescent molecular probes, due to limited brightness, do not allow imaging individual biomolecules directly in living cells, whereas bright fluorescent nanoparticles are unable to respond to single molecular stimuli and their inorganic core is not biodegradable. The aim of BrightSens is to develop ultrabright fluorescent organic nanoparticles (FONs) capable to convert single molecular stimuli into collective turn-on response of >100 encapsulated dyes, and to apply them in amplified molecular sensing of specific targets at the cell surface (receptors) and in the cytosol (mRNA). The project is composed of three work packages. (1) Synthesis of FONs: Dye-doped polymer and micellar FONs will be obtained by self-assembly. Molecular design of dyes and the use of bulky hydrophobic counterions will enable precise control of dyes organization inside FONs, which will resolve the fundamental problems of self-quenching and cooperative on/off switching in dye ensembles. (2) Synthesis of nanoprobes: Using cooperative Forster Resonance Energy Transfer from FONs to originally designed acceptor-sensor unit, we propose synthesis of the first nanoprobes that (a) undergo complete turn-on or colour switch in response to single molecular targets and (b) harvest light energy into photochemical disruption of cell membrane barriers. (3) Cellular applications: The obtained nanoprobes will be applied in 2D and 3D cultures of cancer cells for background-free single-molecule detection of membrane receptors and intracellular mRNA, which are important markers of cancer and apoptosis. An original concept of amplified photochemical internalization is proposed to trigger by light entry of nanoprobes into the cytosol. This high-risk/high-gain multidisciplinary project will result in new organic nanomaterials with unique photophysical properties that will enable visualization of biomolecules at work in living cells with expected impact on cancer research.
Champ scientifique
- natural sciencesbiological sciencesbiochemistrybiomoleculesnucleic acids
- natural scienceschemical sciencesphysical chemistryphotochemistry
- natural scienceschemical sciencespolymer sciences
- natural sciencesbiological sciencesbiochemistrybiomoleculeslipids
- engineering and technologynanotechnologynano-materials
Programme(s)
Régime de financement
ERC-COG - Consolidator GrantInstitution d’accueil
67081 Strasbourg
France