JCJC SIMI 7 - JCJC - SIMI 7 - Chimie moléculaire, organique, de coordination, catalyse et chimie biologique

Cinnamic-based Turn-ON Fluorescent tools via 2-photon excitation – CiTrON-Fluo

Cinnamic-based Turn-ON Fluorescent Tools using Two-photon excitation

The design of fluorescence tools is an ever-expanding research area in the chemical and biological sciences. The exploration and control of biological processes in a spatiotemporal manner relies increasingly on fluorescence, but the chemical tool kit assembled to date is still unfit to address the multitude of issues arising from the highly complicated nature of living systems. Thus, there is currently a high demand for more sensitive, suitable fluorescent compounds for in vivo applications.

The design, in a rationale fashion, of such cinnamic-based two-photon sensitive tools exhibiting a wide scope of in vivo applications would constitute a real breakthrough in this research field.

Through this proposal, we precisely intend to provide new, alternative and complementary sets of fluorogenic tools that are non- (or weakly) fluorescent in their native forms (OFF state) and whose turn-ON fluorescence is triggered by light excitation. Of particular note is that our attention will be focused on turn-ON fluorescence via two-photon excitation, which exhibits remarkable advantages in view of in vivo applications. Starting from the observation that the o-hydroxycinnamyl platform is quite underestimated notwithstanding its promising feature as a fluorescent phototrigger, we first ambition to raise value of this platform through improving its performance in terms of optical, photochemical as well as physicochemical properties (Objective 1). Furthermore, we would like to examine the potential of the o-hydroxycinnamyl platform as a light-activatable sensitizer for luminescent lanthanide complexes (Objective 2). From a synthetic viewpoint, another significant advantage of the o-hydroxycinnamyl platform is its simple and rational accessiblity in few steps from commercially available and quite cheap materials. Finally, the properties of all envisaged fluorogenic tools will be optimized to such an extent that they will be implemented to cancer biology as cell imaging probes and drug-delivery systems with fluorescence reporting. In that purpose, multicellular tumour spheroids will be utilized as original and pertinent three-dimensional models of cancer cells (Objective 3). <br /> <br />If successful, this chemical biology-oriented project will supply both imaging and drug-delivery circles with appropriate fluorescent tools. <br />

The methods/technologies used to bring this multidisciplinary project to fruition are the following:
i) modern/standard methods of organic synthesis required to prepare the envisaged fluorogenic scaffolds,
ii) standard methods of photophysics and physicochem required to characterize the so-prepared scaffolds and further evaluate their photophysical/physicochemical profile,
iii) modern methods of imaging and cancer biology in order to evaluate/visualize the potential of our fluorogenic tools as cell imaging probes as well as drug-delivery systems with fluorescence reporting.

At this stage of the project, the most salient result relates to the proof-of-principle regarding the luminescence Turn-ON of a lanthanide complex bearing an o-hydroxycinnamyl residue as a phototriggerable sensitizer (Objective 2). The principle is currently evaluated under a two-photon excitation mode bfeore being implemented for biological applications as cell imaging probes.

Chance of exploring/analyzing and controlling biological processes in a spatiotemporal fashion is a permanent «big deal« challenge for chemists and biologists. Thus the design, at best in a rationale fashion, of the prepared fluorogenic tools exhibiting a wide scope of in vivo applications would for sure constitute a real breakthrough in this research field. This high-impact and fascinating challenge is the main goal of the present proposal.
Furthermore, given that the fluorogenic tools we are developing are of high interest for pharmaceutical industry (especially our drug-delivery systems with fluorescence reporting), the first biological tests will rapidly tell us if our tools are worth being patented, an opportunity that we will not miss.
Finally, the targeted ability of our tools for controlling the drug dosing in terms of quantity, location and time is of high relevance in health area thus leading to evident social and economic consequences.

INTERNATIONAL
Oral comm
1. CHASSAING S. (Invited Lecture) Photoactivatable Fluorescent Tools & Organic Synthesis in Zeolites, Sfax (Tunisia), December 19th 2014
2. CHAABOUNI S., FRANCOIS A., ABID S., LOBJOIS V., GALAUP C. & CHASSAING S., En Route to Cinnamic-Based Turn-ON Fluorescent Tools, 6th Days of Organic Chemistry (JCO 2014), Hammamet (Tunisia), September 12-14th 2014

Posters
1. CHAABOUNI S., FRANCOIS A., ABID S., LOBJOIS V. , GALAUP C., CHASSAING S., Lanthanide(III)-Complexes Bearing an o-Hydroxycinnamyl Residue as a Novel Class of Photoactivatable Luminescent Probes, 18th JNC, Monastir (Tunisia), December 21-23rd 2014 (prix du meilleur poster)
2. CHASSAING S., LOBJOIS V., FRANCOIS A., DESLANDES S., CHAABOUNI S., GALAUP C., LORENZO C., Cinnamic-Based Turn-ON Fluorescent Tools using Two-Photon Excitation, 15th Tetrahedron Symposium - Challenges in Bioorganic & Organic Medicinal Chemistry, London (UK), June 24-27th 2014
3. LOBJOIS V., GALAUP C., LORENZO C., CHASSAING S., En Route to Cinnamic-Based Turn-ON Fluorescent Tools, 4th Biosensors Meeting, Bordeaux (France), May 22nd-23rd 2014

NATIONAL

Oral comm
1. CHASSAING S., Fluorescence par Photoactivation & Catalyse par les Zéolithes, Symposium RMN, Toulouse, June 17th 2014

Posters
1. FRANCOIS A., CHAABOUNI S., DESLANDES S., ABID S., LOBJOIS V. , GALAUP C., CHASSAING S., Lanthanide(III)-Complexes Bearing an o-Hydroxycinnamyl Residue as a Novel Class of Photoactivatable Luminescent Probes, Journées TGSO, Toulouse, December 26-28th 2014
2. CHASSAING S. et al., Europium(III)-Complexes Bearing an o-Hydroxycinnamyl Residue as a Novel Class of Photoactivatable Luminescent Probes, XXIème Journée IRPF, Castres, September 26th 2014
3. CHASSAING S. et al., Novel Cinnamic-Based Fluorescent Tools using Two-Photon Excitation - From Synthesis to Phtophysical/Physicochemical/Biological Evaluation, XXVIIème Journée Chimie-Biologie-Santé, Toulouse, April 11th 2014

The design of fluorescence tools is an ever-expanding research area in the chemical and biological sciences. The exploration, understanding and control of biological processes in a spatiotemporal manner relies increasingly on fluorescence, but the chemical tool kit assembled to date is still unfit to address the multitude of issues arising from the highly complicated nature of living systems. Thus, there is currently a high demand for more sensitive, more versatile and more suitable fluorescent compounds for in vivo applications.

Through this proposal, we precisely intend to provide new, alternative and complementary sets of fluorogenic tools that are non- (or weakly) fluorescent in their native forms (OFF state) and whose turn-ON fluorescence is triggered by light excitation. Of particular note is that our attention will be focused on turn-ON fluorescence via two-photon excitation, which exhibits remarkable advantages in view of in vivo applications (ie, in-depth tissue penetration, low phototoxicity, very fine spatiotemporal control). Starting from the observation that the o-hydroxycinnamyl platform is quite underestimated notwithstanding its promising feature as a fluorescent phototrigger, we first ambition to raise value of this platform through improving its performance in terms of optical, photochemical as well as physicochemical properties. Furthermore, we would like to examine the potential of the o-hydroxycinnamyl platform as a light-activatable sensitizer for luminescent lanthanide complexes. The advantages of the so-designed novel class of turn-ON fluorogenic tools include i) near-infrared fluorescence emission, ii) long-emission lifetime, and iii) high resistance to photobleaching. From a synthetic viewpoint, another significant advantage of the o-hydroxycinnamyl platform is its simple and rational accessiblity in few steps from commercially available and quite cheap materials. Finally, the properties of all envisaged fluorogenic tools will be optimized to such an extent that they will be implemented to cancer biology as cell imaging probes and drug-delivery systems with fluorescence reporting. In that purpose, multicellular tumour spheroids will be utilized as original and pertinent three-dimensional models of cancer cells.

If successful, this chemical biology-oriented project will supply both imaging and drug-delivery circles with appropriate fluorescent tools.

Project coordinator

Monsieur Stefan CHASSAING (Institut des Technologies Avancées en sciences du Vivant) – chassaing@unistra.fr

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

ITAV USR3505 Institut des Technologies Avancées en sciences du Vivant

Help of the ANR 169,936 euros
Beginning and duration of the scientific project: September 2013 - 24 Months

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