Chemical Biology

Team Composition

P. I. Dalko, DR

Permanent Staff

H. Dhimane, Pr
A. Maruani, CR
D. Rigault, Tech.

Non Permanent Staff
PhD Students

C. Attiach
E. Brosset-Heckel

F. Ben Khelifa

Controlling Cellular Functions by Light

The control of cellular functions by light is a recent development in cellular biology, physiology and neurosciences: light-sensitive silencing functions of small molecules, such as amino acids, and nucleic acids are cleaved / activated irreversibly by photolysis allowing to trigger perturbations in cells and tissues at the molecular level by site-selective interactions with high temporal resolution and at controlled ligand concentrations.

We are developing aminoquinoline (AQ) based photo-cleavable probes first introduced by the Dore group. AQ caging groups have larger TP cross-sections than the nitrobenzyl or nitroindolinyl cages, and show fast fragmentation kinetics in physiological solution, high near UV uncaging sensitivity, good water solubility and low fluorescence. We have optimized the one- and two-photon excitation and physical properties of the AQs extensively to give a small chemical library of ‘caging’ groups, and applications of the optimized probes in different area of neurosciences is underway.

Smart Nanomaterials for “On Demand” Drug Delivery

Drug toxicity stays a common and significant health problem. The systemic toxicity of the drug could be eventually diminished by administering in a detoxified form (such as in classical pro-drug strategies) and activate only (and exclusively) on the desired site. From the considerable arsenal of the prodrug strategy, the delivery of active molecules from nano-sized organic or inorganic nanocarriers that immobilize or encapsulate a larger amount of drugs promises breakthrough. Polymer-based nanocarriers (polymersomes, Ps) have proven their utility to deliver therapeutic agents to specific tissues/organs. We are developing sensitized polymersomes, that may encapsulate and transport a virtually unlimited variety and complexity of organic / inorganic substrates in otherwise inaccessible (body)spaces and can deliver the payload by an exogenous or endogenous signal with real-time imaging ability.

1. Petit, M.; Bort, G.; Doan, B.-T.; Sicard, C.; Ogden, D.; Scherman, D.; Ferroud C.; Dalko, P. I. “X-Ray photolysis to release ligands from ‘caged’ reagents by an intramolecular MRI-sensitive antenna.” Angew. Chem. Int. Ed. 2011, 50, 9708–9711
2. G. Bort, T. Gallavardin, D. Ogden, P. I. Dalko “From One-Photon to Two-Photon Probes: ‘Caged’ Compounds, Actuators and Photoswitches”, Angew. Chem. Int. Ed. 2013, 52, 4526-4537.
3. Dunkel, P.; Hayat, Z.; Barosi, A.; Bchellaoui, N.; Dhimane, H.; Dalko, P. I.; El Abed, A. I. “Photolysis-driven merging of microdroplets in microfluidic chambers.” Lab Chip. 2016, 16, 1484-1491.
4. Tran, C.; Berqouch, N.; Dhimane, H.; Clermont, G.; Blanchard-Desce, M.; Ogden, D.; Dalko, P. I. “Quinoline-Derived Two-Photon Sensitive Quadrupolar Probes” Chem. Eur. J. 2017, 23, 1860-1868.
5. P. Dunkel, A. Barosi, H. Dhimane, F. Maurel, P. I. Dalko “Photoinduced Electron Transfer (PET)‐Mediated Fragmentation of Picolinium‐Derived Redox Probes”  Chem. Eur. J., 2018, 24, 12920– 12931.

Chemical Biology

Team composition

Permanent Staff

Peter I. Dalko
Director of Research, CNRS

H. Dhimane, Pr
D. Rigault, Tech.

Non Permanent Staff

A. Kumar, Post-doc
R. Guermazi, ATER

PhD Students

Team Description

Controlling Cellular Functions by Light

The control of cellular functions by light is a recent development in cellular biology, physiology and neurosciences: light-sensitive silencing functions of small molecules, such as amino acids, and nucleic acids are cleaved / activated irreversibly by photolysis allowing to trigger perturbations in cells and tissues at the molecular level by site-selective interactions with high temporal resolution and at controlled ligand concentrations.

We are developing aminoquinoline (AQ) based photo-cleavable probes first introduced by the Dore group. AQ caging groups have larger TP cross-sections than the nitrobenzyl or nitroindolinyl cages, and show fast fragmentation kinetics in physiological solution, high near UV uncaging sensitivity, good water solubility and low fluorescence. We have optimized the one- and two-photon excitation and physical properties of the AQs extensively to give a small chemical library of ‘caging’ groups, and applications of the optimized probes in different area of neurosciences is underway.

Smart Nanomaterials for “On Demand” Drug Delivery

Drug toxicity stays a common and significant health problem. The systemic toxicity of the drug could be eventually diminished by administering in a detoxified form (such as in classical pro-drug strategies) and activate only (and exclusively) on the desired site. From the considerable arsenal of the prodrug strategy, the delivery of active molecules from nano-sized organic or inorganic nanocarriers that immobilize or encapsulate a larger amount of drugs promises breakthrough. Polymer-based nanocarriers (polymersomes, Ps) have proven their utility to deliver therapeutic agents to specific tissues/organs. We are developing sensitized polymersomes, that may encapsulate and transport a virtually unlimited variety and complexity of organic / inorganic substrates in otherwise inaccessible (body)spaces and can deliver the payload by an exogenous or endogenous signal with real-time imaging ability.

Main publications

1. Petit, M.; Bort, G.; Doan, B.-T.; Sicard, C.; Ogden, D.; Scherman, D.; Ferroud C.; Dalko, P. I. “X-Ray photolysis to release ligands from ‘caged’ reagents by an intramolecular MRI-sensitive antenna.” Angew. Chem. Int. Ed. 2011, 50, 9708–9711
2. G. Bort, T. Gallavardin, D. Ogden, P. I. Dalko “From One-Photon to Two-Photon Probes: ‘Caged’ Compounds, Actuators and Photoswitches”, Angew. Chem. Int. Ed. 2013, 52, 4526-4537.
3. Dunkel, P.; Hayat, Z.; Barosi, A.; Bchellaoui, N.; Dhimane, H.; Dalko, P. I.; El Abed, A. I. “Photolysis-driven merging of microdroplets in microfluidic chambers.” Lab Chip. 2016, 16, 1484-1491.
4. Tran, C.; Berqouch, N.; Dhimane, H.; Clermont, G.; Blanchard-Desce, M.; Ogden, D.; Dalko, P. I. “Quinoline-Derived Two-Photon Sensitive Quadrupolar Probes” Chem. Eur. J. 2017, 23, 1860-1868.
5. P. Dunkel, A. Barosi, H. Dhimane, F. Maurel, P. I. Dalko “Photoinduced Electron Transfer (PET)‐Mediated Fragmentation of Picolinium‐Derived Redox Probes”  Chem. Eur. J., 2018, 24, 12920– 12931.