Descripción del proyecto
Nanosondas fluorescentes para biosensores amplificados
Los científicos exploran las funciones celulares analizando cómo interactúan entre sí diversos componentes, como las biomoléculas y múltiples orgánulos. Por lo general, esto implica rastrear y visualizar biomoléculas individuales dentro de células vivas utilizando sondas fluorescentes. Sin embargo, la limitada luminosidad de las sondas fluorescentes existentes dificulta la detección molecular, lo que plantea problemas técnicos. El equipo del proyecto BrightSens, financiado por el Consejo Europeo de Investigación, desarrollará nanopartículas orgánicas fluorescentes ultrabrillantes capaces de convertir un único evento de reconocimiento molecular en una respuesta óptica de cientos de colorantes encapsulados. Así, se propone un concepto de amplificación de la señal basado en nanopartículas fluorescentes para aumentar la sensibilidad de la biodetección. Estas nanopartículas encierran un inmenso potencial para la detección de receptores de membrana y ARN intracelular en células cancerosas, abriendo así nuevas oportunidades en la investigación biomédica.
Objetivo
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.
Ámbito científico
- natural sciencesbiological sciencesbiochemistrybiomoleculesnucleic acids
- natural scienceschemical sciencesphysical chemistryphotochemistry
- natural scienceschemical sciencespolymer sciences
- natural sciencesbiological sciencesbiochemistrybiomoleculeslipids
- engineering and technologynanotechnologynano-materials
Programa(s)
Régimen de financiación
ERC-COG - Consolidator GrantInstitución de acogida
67081 Strasbourg
Francia