H2020Individual fellowship2017–2019

NanoOxySens · Luminescent Polymer Nanoparticles with Aza-BODIPYs, Porphyrins and their Metal Complexes for FRET Mediated Ratiometric Oxygen Sensing

Horizon 2020 — Marie Skłodowska-Curie Actions

Duration
2017-05-15 → 2019-05-14
EU contribution
€185,076
Participants
1
Scheme
MSCA-IF-EF-ST

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Results in brief

Luminescent Polymer Nanoparticles with Aza-BODIPYs, Porphyrins and their Metal Complexes for FRET Mediated Ratiometric Oxygen Sensing

What is the problem/issue being addressed? Detection of early stage of cancer and monitoring its response to a treatment is a major challenge in the research on diagnostics and therapy. One of the pathways which aid the early stage diagnosis of tumours is to detect and image the hypoxic regions in cells, which normally exist as oxygen gradients. The accurate detection and imaging of the molecular oxygen requires robust, safe and sensitive probes. Hence, the major challenge to be addressed here is to convert ultrabright dye-loaded polymeric nanoparticles into ratiometric sensors for the detection and imaging of hypoxic regions in cancer cells. Second, it is challenging to generate a stable oxygen gradient conditions for evaluation of the probes and modelling hypoxia conditions in tumours. Why is it important for society? The limitation and failure of early stage detection and diagnosis leads to increased risks of inefficient therapy of cancer patients, which constitute an important concern for the society. Hypoxia is a pathophysiological condition, commonly referred as a state of reduced oxygen tension, which is characteristic feature of tumours and other pathologies. Accurate detection and imaging of hypoxic regions can be a solution for the early stage diagnosis of various tumours. Here, we successfully demonstrated the FRET-based ultrabright polymeric nanoparticles for the ratiometric detection and imaging of oxygen gradients in cancer cells, which we believe can address the concern of early stage cancer diagnosis in the future and thus can improve the public health. The developed probes have a good potential for commercialization as high-tech products for biomedical applications. What are the overall objectives? The principal objective of the project was to develop an ultrabright polymeric nanoprobe for the FRET-mediated ratiometric detection of molecular oxygen. In particular, to build the nanoprobes we aimed to use (i) biocompatible polymer to address the issues of safety; (ii) high concentration with loaded fluorescent dyes with the bulky hydrophobic counterions to ensure efficient fluorescence and (iii) phosphorescent FRET acceptor to ensure ratiometric response to oxygen. The second objective is accurate detection of oxygen gradients in cancer cells. Specifically, we aimed to develop a simple and convenient microfluidic chamber with a stable oxygen gradient and compatible with fluorescence imaging of cancer cells and our polymeric nanoprobes.

Data: CORDIS, © European Union

Project objective

This proposed Fellowship brings together an Experienced Researcher from India with expertise in the synthesis of photosensitizers and their photophysical characterization, tuning the excited-state properties, investigation of their photophysics and photobiology with an internationally recognized Host Laboratory in France with expertise in designing fluorescent molecular and nanoparticle probes for bioimaging. This project will provide (i) interdisciplinary training of highest quality to become an outstanding scientist with excellent publication record; (ii) enhance European excellence in organic synthesis, nanosciences and biophotonics. The aim of the research project is to obtain ratiometric probes for molecular oxygen based on biodegradable polymeric nanoparticles (NPs) bearing far-red/near-infrared absorbing triplet sensitizers such as aza-BODIPYs, porphyrins and corresponding metal complexes. The project involves the synthesis of phosphorescent dyes (aza-BODIPY/porphyrins) and formulation of polymeric NPs encapsulating these dyes. The development of ultra-bright polymer nanoparticles, an innovative method recently discovered in the Host Laboratory, will enable the development of novel dual emissive polymeric NPs with the triplet sensitizers. In our design, fluorescent NPs excite triplet sensitizers through energy transfer (FRET), resulting in dual emission: fluorescence of NPs and phosphoresce of the sensitizer. Only phosphorescence of FRET acceptor is sensitive to molecular oxygen (3O2), which provides the mechanism of dual colour ratiometric response to oxygen. The approach will be further validated in solutions and in living cells. The obtained nanoprobes for oxygen will be applied to living cell and (in collaboration) to whole animals. It is our strong conviction that the possibilities of this multidisciplinary chemistry are enormous, and the end result will be the development of a simple nano-device for molecular oxygen build from biodegradable materials.

Original text from CORDIS.

Participants

  • UNIVERSITE DE STRASBOURG · StrasbourgCoordinatorFrance

Links

Data: CORDIS, © European Union