Chargé de Recherche CNRS
ENS – Département de chimie
24 rue Lhomond, 75005 Paris
Email: nicolas.delsuc@ens.psl.eu
Phone: +33 144322424
Office: E037a
Our website: https://ens-bic.fr/
Short bio
I have been trained in chemistry at Bordeaux University. I did a PhD from 2004 to 2007 in supramolecular chemistry under the supervision of Dr. Ivan Huc. I worked on the development of proteomimetic structures using abiotic foldamers. I then obtained a fellowship from the Japan Society for the Promotion of Sciences (JSPS) to join the group of Prof. Itaru Hamachi at Kyoto University where I worked on new peptidyl receptors for peptide recognition. In 2009, I came back to France as temporary lecturer (ATER) at the Laboratoire des Biomolécules (LBM, UMR 7203), where I worked with Prof. Philippe Karoyan to develop foldamers based on proline derivatives. I have been appointed as CNRS researcher in 2010 and joined the group of Clotilde Policar at the LBM. I first worked on the conjugation of bioactive molecules with peptide to enhance their penetration and bioavaibality as well on the development of multimodal metal-based probes. Now I want to combine peptide and metal ions to synergistically take advantages of the properties of both classes of molecules by developing new peptidyl metalloprobes and metallodrugs.
Education and professional experience
- Sept 2020-2022: Assitant Professor associate. ENS
- Oct 2010-now: Associate researcher. Laboratoire des BioMolécules, UMR7203 CNRS-SU-ENS. In the Inorganic Cellular Chemistry group within the team 1.
- Sept 2009-Sept 2010: Teaching assistant. Laboratoire des BioMolécules, UMR7203 UPMC-ENS. In the group of P. Karoyan, « Conception of enzyme mimics with foldamers »
- Nov 2007-Jul 2009: Post-doctoral fellow of the JSPS. Kyoto University, Japan. In the group of I. Hamachi. « Development of molecular receptors for specific peptides recognition »
- Oct 2004-Oct 2007: PhD in Organic chemistry, Bordeaux1 University under the supervision of I. Huc. »Development of proteomimetic tertiary structures with aromatic oligoamide foldamers »
- Sept 2005- Sept 2007: M.Sc. in Organic chemistry, Bordeaux1 University
Research interests
- Development of peptidyl metal complexes mimicking metalloenzymes
- Development of metal-centered probes for bio-imaging or diagnostic
Awards, distinctions and grants
- 2024: ITMO PCSI
- 2023: Arc Foundation grant
- 2016: ANR JCJC
- 2007: JSPS Postodoctoral Fellowship
Supervised PhD and post-doctoral students
- Current: Nader Balbali (2023-), Willem Kauffeld (2024-)
- Formers: Gabrielle Schanne (2019-2022), Martha Zoumpoulaki (2017-2021), Koudedja Coulibaly (2017-2020), Amandine Vincent (2016-2019), Emilie Mathieu (2014-2017), Sarah Hostachy (2012-2015), May Lee Low (2011-2014, cotutelle with Malaysia), Anne-Sophie Bernard (2010-2014)
Publications
2025 |
Angle-dependent spin crossover properties in polymorphic iron (ii) complexes based on pyridine--triazole derivatives Article de journal Emmelyne Cuza; Nicolas Delsuc; Jer^ome Marrot; William Shepard; Clotilde Policar; Christian Serre; Antoine Tissot Dalton Transactions, 54 (15), p. 6274–6280, 2025. @article{cuza2025angled, title = {Angle-dependent spin crossover properties in polymorphic iron (ii) complexes based on pyridine--triazole derivatives}, author = {Emmelyne Cuza and Nicolas Delsuc and Jer{^o}me Marrot and William Shepard and Clotilde Policar and Christian Serre and Antoine Tissot}, year = {2025}, date = {2025-01-01}, journal = {Dalton Transactions}, volume = {54}, number = {15}, pages = {6274--6280}, publisher = {Royal Society of Chemistry}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Angle-dependent spin crossover properties in polymorphic iron (ii) complexes based on pyridine--triazole derivatives Article de journal Emmelyne Cuza; Nicolas Delsuc; Jer^ome Marrot; William Shepard; Clotilde Policar; Christian Serre; Antoine Tissot Dalton Transactions, 54 (15), p. 6274–6280, 2025. @article{cuza2025anglec, title = {Angle-dependent spin crossover properties in polymorphic iron (ii) complexes based on pyridine--triazole derivatives}, author = {Emmelyne Cuza and Nicolas Delsuc and Jer{^o}me Marrot and William Shepard and Clotilde Policar and Christian Serre and Antoine Tissot}, year = {2025}, date = {2025-01-01}, journal = {Dalton Transactions}, volume = {54}, number = {15}, pages = {6274--6280}, publisher = {Royal Society of Chemistry}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Angle-dependent spin crossover properties in polymorphic iron (ii) complexes based on pyridine--triazole derivatives Article de journal Emmelyne Cuza; Nicolas Delsuc; Jer^ome Marrot; William Shepard; Clotilde Policar; Christian Serre; Antoine Tissot Dalton Transactions, 54 (15), p. 6274–6280, 2025. @article{cuza2025angleb, title = {Angle-dependent spin crossover properties in polymorphic iron (ii) complexes based on pyridine--triazole derivatives}, author = {Emmelyne Cuza and Nicolas Delsuc and Jer{^o}me Marrot and William Shepard and Clotilde Policar and Christian Serre and Antoine Tissot}, year = {2025}, date = {2025-01-01}, journal = {Dalton Transactions}, volume = {54}, number = {15}, pages = {6274--6280}, publisher = {Royal Society of Chemistry}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Angle-dependent spin crossover properties in polymorphic iron (ii) complexes based on pyridine--triazole derivatives Article de journal Emmelyne Cuza; Nicolas Delsuc; Jer^ome Marrot; William Shepard; Clotilde Policar; Christian Serre; Antoine Tissot Dalton Transactions, 54 (15), p. 6274–6280, 2025. @article{cuza2025angle, title = {Angle-dependent spin crossover properties in polymorphic iron (ii) complexes based on pyridine--triazole derivatives}, author = {Emmelyne Cuza and Nicolas Delsuc and Jer{^o}me Marrot and William Shepard and Clotilde Policar and Christian Serre and Antoine Tissot}, year = {2025}, date = {2025-01-01}, journal = {Dalton Transactions}, volume = {54}, number = {15}, pages = {6274--6280}, publisher = {Royal Society of Chemistry}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Kinetic Redox Shotgun Proteomics Reveals Specific Lipopolysaccharide Effects on Intestinal Epithelial Cells, Mitigated by a Mn Superoxide Dismutase Mimic Article de journal Martha Zoumpoulaki; Giovanni Chiappetta; Jean Bouvet; Namita-Raju John; Gabrielle Schanne; Pauline Gehan; Samuel Diebolt; Shakir Shakir; Elodie Quévrain; Emilie Mathieu; Sylvie Demignot; Philippe Seksik; Nicolas Delsuc; Joelle Vinh; Clotilde Policar Angewandte Chemie International Edition, n/a (n/a), p. e202422644, 2025. @article{https://doi.org/10.1002/anie.202422644, title = {Kinetic Redox Shotgun Proteomics Reveals Specific Lipopolysaccharide Effects on Intestinal Epithelial Cells, Mitigated by a Mn Superoxide Dismutase Mimic}, author = {Martha Zoumpoulaki and Giovanni Chiappetta and Jean Bouvet and Namita-Raju John and Gabrielle Schanne and Pauline Gehan and Samuel Diebolt and Shakir Shakir and Elodie Qu\'{e}vrain and Emilie Mathieu and Sylvie Demignot and Philippe Seksik and Nicolas Delsuc and Joelle Vinh and Clotilde Policar}, url = {https://onlinelibrary.wiley.com/doi/abs/10.1002/anie.202422644}, doi = {https://doi.org/10.1002/anie.202422644}, year = {2025}, date = {2025-01-01}, journal = {Angewandte Chemie International Edition}, volume = {n/a}, number = {n/a}, pages = {e202422644}, abstract = {Abstract Overproduction of reactive oxygen species and antioxidant superoxide dismutases (SOD1, SOD2) dysregulation contribute to chronic inflammation such as generated in inflammatory bowel diseases (IBD). A kinetic redox shotgun proteomic strategy (OcSILAC for Oxidized cysteine Stable Isotope Labelling by Amino acids in Cell culture) was used to explore the lipopolysaccharide (LPS) effects including LPS-induced oxidation and inflammation cascades on a dedicated intestinal epithelial cell line (HT29-MD2) together with the potential mitigating role of a Mn-based SOD-mimic Mn1. While LPS induced transient oxidative damages at early times (15 min), cells incubated with Mn1 showed, in this time frame, a significantly reduced cysteine oxidation, highlighting Mn1 antioxidant properties. Over time, cysteine oxidation of LPS-treated cells was counteracted by an overexpression of antioxidant proteins (SOD1, NQO1) and a late (6 h) preponderant increase in SOD2 level. Mn1, when co-incubated with LPS, attenuated the level of most LPS-modified proteins, that is, proteins involved in the inflammatory response. Our results highlight Mn1 as a potentially effective antioxidant and anti-inflammatory agent to consider in the treatment of IBD, as well as a useful tool for exploring the interconnection between oxidative stress and inflammation.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Abstract Overproduction of reactive oxygen species and antioxidant superoxide dismutases (SOD1, SOD2) dysregulation contribute to chronic inflammation such as generated in inflammatory bowel diseases (IBD). A kinetic redox shotgun proteomic strategy (OcSILAC for Oxidized cysteine Stable Isotope Labelling by Amino acids in Cell culture) was used to explore the lipopolysaccharide (LPS) effects including LPS-induced oxidation and inflammation cascades on a dedicated intestinal epithelial cell line (HT29-MD2) together with the potential mitigating role of a Mn-based SOD-mimic Mn1. While LPS induced transient oxidative damages at early times (15 min), cells incubated with Mn1 showed, in this time frame, a significantly reduced cysteine oxidation, highlighting Mn1 antioxidant properties. Over time, cysteine oxidation of LPS-treated cells was counteracted by an overexpression of antioxidant proteins (SOD1, NQO1) and a late (6 h) preponderant increase in SOD2 level. Mn1, when co-incubated with LPS, attenuated the level of most LPS-modified proteins, that is, proteins involved in the inflammatory response. Our results highlight Mn1 as a potentially effective antioxidant and anti-inflammatory agent to consider in the treatment of IBD, as well as a useful tool for exploring the interconnection between oxidative stress and inflammation. |
SOD mimics delivered to the gut using lactic acid bacteria mitigate the colitis symptoms in a mouse model of Inflammatory Bowel Diseases Article de journal Gabrielle Schanne; Amandine Vincent; Florian Chain; Pauline Ruffié; Célia Carbonne; Elodie Quévrain; Emilie Mathieu; Alice Balfourier; Luis G Bermúdez-Humarán; Philippe Langella; Sophie Thenet; Véronique Carrière; Nassim Hammoudi; Magali Svreck; Sylvie Demignot; Philippe Seksik; Clotilde Policar; Nicolas Delsuc Free Radical Research, p. 1–16, 2025, (PMID: 40079422). @article{Schanne13032025, title = {SOD mimics delivered to the gut using lactic acid bacteria mitigate the colitis symptoms in a mouse model of Inflammatory Bowel Diseases}, author = {Gabrielle Schanne and Amandine Vincent and Florian Chain and Pauline Ruffi\'{e} and C\'{e}lia Carbonne and Elodie Qu\'{e}vrain and Emilie Mathieu and Alice Balfourier and Luis G Berm\'{u}dez-Humar\'{a}n and Philippe Langella and Sophie Thenet and V\'{e}ronique Carri\`{e}re and Nassim Hammoudi and Magali Svreck and Sylvie Demignot and Philippe Seksik and Clotilde Policar and Nicolas Delsuc}, url = {https://doi.org/10.1080/10715762.2025.2478121}, doi = {10.1080/10715762.2025.2478121}, year = {2025}, date = {2025-01-01}, journal = {Free Radical Research}, pages = {1--16}, publisher = {Taylor & Francis}, note = {PMID: 40079422}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
2024 |
Cellular evaluation of superoxide dismutase mimics as catalytic drugs: Challenges and opportunities Article de journal Gabrielle Schanne; Sylvie Demignot; Clotilde Policar; Nicolas Delsuc Coordination Chemistry Reviews, 514 , p. 215906, 2024, ISSN: 0010-8545. @article{SCHANNE2024215906, title = {Cellular evaluation of superoxide dismutase mimics as catalytic drugs: Challenges and opportunities}, author = {Gabrielle Schanne and Sylvie Demignot and Clotilde Policar and Nicolas Delsuc}, url = {https://www.sciencedirect.com/science/article/pii/S0010854524002522}, doi = {https://doi.org/10.1016/j.ccr.2024.215906}, issn = {0010-8545}, year = {2024}, date = {2024-01-01}, journal = {Coordination Chemistry Reviews}, volume = {514}, pages = {215906}, abstract = {Oxidative stress is known to be associated with many pathologies including inflammation, cancer, diabetes, etc. However, oxidative stress resulting from the imbalance between reactive oxygen species flows and antioxidant defenses has been largely overlooked so far as a therapeutic target. Among antioxidant defenses, superoxide dismutases (SOD) are metalloenzymes that catalyze efficiently the dismutation of superoxide, the first reactive oxygen species resulting from the monoelectronic reduction of dioxygen. Superoxide, as a quite reactive chemical species, is a transient species. So, the cellular evaluation of metal complexes mimicking SOD (SOD mimics) in cellular models can be particularly tedious and calls for multiple direct and indirect strategies including probes and biochemical assays. This review highlights methods and assays to evaluate in cells SOD mimics, a new class of catalytic antioxidants.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Oxidative stress is known to be associated with many pathologies including inflammation, cancer, diabetes, etc. However, oxidative stress resulting from the imbalance between reactive oxygen species flows and antioxidant defenses has been largely overlooked so far as a therapeutic target. Among antioxidant defenses, superoxide dismutases (SOD) are metalloenzymes that catalyze efficiently the dismutation of superoxide, the first reactive oxygen species resulting from the monoelectronic reduction of dioxygen. Superoxide, as a quite reactive chemical species, is a transient species. So, the cellular evaluation of metal complexes mimicking SOD (SOD mimics) in cellular models can be particularly tedious and calls for multiple direct and indirect strategies including probes and biochemical assays. This review highlights methods and assays to evaluate in cells SOD mimics, a new class of catalytic antioxidants. |
Piezoelectric and microfluidic tuning of an infrared cavity for vibrational polariton studies Article de journal Wei Wang; Jaime de la Fuente Diez; Nicolas Delsuc; Juan Peng; Riccardo Spezia; Rodolphe Vuilleumier; Yong Chen Lab Chip, p. -, 2024. @article{D3LC01101A, title = {Piezoelectric and microfluidic tuning of an infrared cavity for vibrational polariton studies}, author = {Wei Wang and Jaime de la Fuente Diez and Nicolas Delsuc and Juan Peng and Riccardo Spezia and Rodolphe Vuilleumier and Yong Chen}, url = {http://dx.doi.org/10.1039/D3LC01101A}, doi = {10.1039/D3LC01101A}, year = {2024}, date = {2024-01-01}, journal = {Lab Chip}, pages = {-}, publisher = {The Royal Society of Chemistry}, abstract = {We developed a microfluidic system for vibrational polariton studies, which consists of two microfluidic chips: one for solution mixing and another for tuning an infrared cavity made of a pair of gold mirrors and a PDMS (polydimethylsiloxane) spacer. We show that the cavity of the system can be accurately tuned with either piezoelectric actuators or microflow-induced pressure to result in resonant coupling between a cavity mode and a variational mode of the solution molecules. Acrylonitrile solutions were chosen to prove the concept of vabriational strong coupling (VSC) of a CN stretching mode with light inside the cavity. We also show that the Rabi splitting energy is linearly proportional to the square root of molecular concentration, thereby proving the relevance and reliability of the system for VSC studies.}, keywords = {}, pubstate = {published}, tppubtype = {article} } We developed a microfluidic system for vibrational polariton studies, which consists of two microfluidic chips: one for solution mixing and another for tuning an infrared cavity made of a pair of gold mirrors and a PDMS (polydimethylsiloxane) spacer. We show that the cavity of the system can be accurately tuned with either piezoelectric actuators or microflow-induced pressure to result in resonant coupling between a cavity mode and a variational mode of the solution molecules. Acrylonitrile solutions were chosen to prove the concept of vabriational strong coupling (VSC) of a CN stretching mode with light inside the cavity. We also show that the Rabi splitting energy is linearly proportional to the square root of molecular concentration, thereby proving the relevance and reliability of the system for VSC studies. |
Clotilde Policar; Nicolas Delsuc; Hél`ene Charlotte Bertrand Comptes Rendus. Chimie, 2024, (Online first). @article{CRCHIM_2024__27_S2_A12_0, title = {Metal complexes in cells: from design of catalytic antioxidants to imaging metal ions and designing metal-based probes in X-ray fluorescence and IR-imaging, a multidisciplinary collaborative journey in bioinorganic chemistry and inorganic chemical biology}, author = {Clotilde Policar and Nicolas Delsuc and H\'{e}l`ene Charlotte Bertrand}, doi = {10.5802/crchim.295}, year = {2024}, date = {2024-01-01}, journal = {Comptes Rendus. Chimie}, publisher = {Acad\'{e}mie des sciences, Paris}, note = {Online first}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
2023 |
Ruthenium(II) polypyridyl complexes as emerging photosensitisers for antibacterial photodynamic therapy Article de journal Ng Xiao Ying; Fong Kar Wai; Kiew Lik Voon; Katrina Chung Pooi Yin; Liew Yun Khoon; Nicolas Delsuc; Mohd Zulkefeli; Low May Lee Journal of Inorganic Biochemistry, p. 112425, 2023, ISSN: 0162-0134. @article{YING2023112425, title = {Ruthenium(II) polypyridyl complexes as emerging photosensitisers for antibacterial photodynamic therapy}, author = {Ng Xiao Ying and Fong Kar Wai and Kiew Lik Voon and Katrina Chung Pooi Yin and Liew Yun Khoon and Nicolas Delsuc and Mohd Zulkefeli and Low May Lee}, url = {https://www.sciencedirect.com/science/article/pii/S0162013423003070}, doi = {https://doi.org/10.1016/j.jinorgbio.2023.112425}, issn = {0162-0134}, year = {2023}, date = {2023-01-01}, journal = {Journal of Inorganic Biochemistry}, pages = {112425}, abstract = {Photodynamic therapy (PDT) has recently emerged as a potential valuable alternative to treat microbial infections. In PDT, singlet oxygen is generated in the presence of photosensitisers and oxygen under light irradiation of a specific wavelength, causing cytotoxic damage to bacteria. This review highlights different generations of photosensitisers and the common characteristics of ideal photosensitisers. It also focuses on the emergence of ruthenium and more specifically on Ru(II) polypyridyl complexes as metal-based photosensitisers used in antimicrobial photodynamic therapy (aPDT). Their photochemical and photophysical properties as well as structures are discussed while relating them to their phototoxicity. The use of Ru(II) complexes with recent advancements such as nanoformulations, combinatory therapy and photothermal therapy to improve on previous shortcomings of the complexes are outlined. Future perspectives of these complexes used in two-photon PDT, photoacoustic imaging and sonotherapy are also discussed. This review covers the literature published from 2017 to 2023.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Photodynamic therapy (PDT) has recently emerged as a potential valuable alternative to treat microbial infections. In PDT, singlet oxygen is generated in the presence of photosensitisers and oxygen under light irradiation of a specific wavelength, causing cytotoxic damage to bacteria. This review highlights different generations of photosensitisers and the common characteristics of ideal photosensitisers. It also focuses on the emergence of ruthenium and more specifically on Ru(II) polypyridyl complexes as metal-based photosensitisers used in antimicrobial photodynamic therapy (aPDT). Their photochemical and photophysical properties as well as structures are discussed while relating them to their phototoxicity. The use of Ru(II) complexes with recent advancements such as nanoformulations, combinatory therapy and photothermal therapy to improve on previous shortcomings of the complexes are outlined. Future perspectives of these complexes used in two-photon PDT, photoacoustic imaging and sonotherapy are also discussed. This review covers the literature published from 2017 to 2023. |
Engineering Peptidyl and Protein Glutathione Peroxidase Mimics Book Chapter Nicolas Delsuc Peptide and Protein Engineering for Biotechnological and Therapeutic Applications, Chapitre Chapter 6, p. 247-278, WORLD SCIENTIFIC, 2023. @inbook{doi:10.1142/9789811261664_0006c, title = {Engineering Peptidyl and Protein Glutathione Peroxidase Mimics}, author = {Nicolas Delsuc}, url = {https://www.worldscientific.com/doi/abs/10.1142/9789811261664_0006}, doi = {10.1142/9789811261664_0006}, year = {2023}, date = {2023-01-01}, booktitle = {Peptide and Protein Engineering for Biotechnological and Therapeutic Applications}, pages = {247-278}, publisher = {WORLD SCIENTIFIC}, chapter = {Chapter 6}, abstract = {The following sections are included: Introduction Mammalian GPx GPx Mimics Conclusion List of Abbreviations References}, keywords = {}, pubstate = {published}, tppubtype = {inbook} } The following sections are included: Introduction Mammalian GPx GPx Mimics Conclusion List of Abbreviations References |
2022 |
Deciphering the Metal Speciation in Low-Molecular-Weight Complexes by IMS-MS: Application to the Detection of Manganese Superoxide Dismutase Mimics in Cell Lysates Article de journal Martha Zoumpoulaki; Gabrielle Schanne; Nicolas Delsuc; Hugues Preud'homme; Elodie Quévrain; Nicolas Eskenazi; Géraldine Gazzah; Regis Guillot; Philippe Seksik; Joelle Vinh; Ryszard Lobinski; Clotilde Policar Angewandte Chemie International Edition, n/a (n/a), p. e202203066, 2022. @article{https://doi.org/10.1002/anie.202203066, title = {Deciphering the Metal Speciation in Low-Molecular-Weight Complexes by IMS-MS: Application to the Detection of Manganese Superoxide Dismutase Mimics in Cell Lysates}, author = {Martha Zoumpoulaki and Gabrielle Schanne and Nicolas Delsuc and Hugues Preud'homme and Elodie Qu\'{e}vrain and Nicolas Eskenazi and G\'{e}raldine Gazzah and Regis Guillot and Philippe Seksik and Joelle Vinh and Ryszard Lobinski and Clotilde Policar}, url = {https://onlinelibrary.wiley.com/doi/abs/10.1002/anie.202203066}, doi = {https://doi.org/10.1002/anie.202203066}, year = {2022}, date = {2022-01-01}, journal = {Angewandte Chemie International Edition}, volume = {n/a}, number = {n/a}, pages = {e202203066}, abstract = {Abstract The detection and quantification of exogenous metal complexes are crucial to understanding their activity in intricate biological media. MnII complexes are difficult to detect and quantify because of low association constants, and high lability. The superoxide dismutase (SOD) mimic (or mimetic) labelled Mn1 is based on a 1,2-di-aminoethane functionalized with imidazole and phenolate and has good intrinsic anti-superoxide, antioxidant and anti-inflammatory activities in lipopolysaccharide (LPS)-activated intestinal epithelial HT29-MD2 cells, similar to that of its propylated analogue labelled Mn1P. Ion mobility spectrometry-mass spectrometry (IMS-MS) is a powerful technique for separating low molecular weight (LMW) metal complexes and can even separate complexes with the same ligand but bound to different divalent metal cations with similar ionic radii. We demonstrated the intracellular presence of the Mn1 and Mn1P complexes, at least partly intact, in lysates of cells incubated with the complexes and estimated the intracellular Mn1P concentration using a Co-13C6 analogue.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Abstract The detection and quantification of exogenous metal complexes are crucial to understanding their activity in intricate biological media. MnII complexes are difficult to detect and quantify because of low association constants, and high lability. The superoxide dismutase (SOD) mimic (or mimetic) labelled Mn1 is based on a 1,2-di-aminoethane functionalized with imidazole and phenolate and has good intrinsic anti-superoxide, antioxidant and anti-inflammatory activities in lipopolysaccharide (LPS)-activated intestinal epithelial HT29-MD2 cells, similar to that of its propylated analogue labelled Mn1P. Ion mobility spectrometry-mass spectrometry (IMS-MS) is a powerful technique for separating low molecular weight (LMW) metal complexes and can even separate complexes with the same ligand but bound to different divalent metal cations with similar ionic radii. We demonstrated the intracellular presence of the Mn1 and Mn1P complexes, at least partly intact, in lysates of cells incubated with the complexes and estimated the intracellular Mn1P concentration using a Co-13C6 analogue. |
Inertness of Superoxide Dismutase Mimics Mn(II) Complexes Based on an Open-Chain Ligand, Bioactivity, and Detection in Intestinal Epithelial Cells Article de journal Gabrielle Schanne; Martha Zoumpoulaki; Géraldine Gazzah; Amandine Vincent; Hugues Preud’homme; Ryszard Lobinski; Sylvie Demignot; Philippe Seksik; Nicolas Delsuc; Clotilde Policar Oxidative Medicine and Cellular Longevity, 2022 , p. e3858122, 2022, ISSN: 1942-0900, (Publisher: Hindawi). @article{schanne_inertness_2022, title = {Inertness of Superoxide Dismutase Mimics Mn(II) Complexes Based on an Open-Chain Ligand, Bioactivity, and Detection in Intestinal Epithelial Cells}, author = {Gabrielle Schanne and Martha Zoumpoulaki and G\'{e}raldine Gazzah and Amandine Vincent and Hugues Preud’homme and Ryszard Lobinski and Sylvie Demignot and Philippe Seksik and Nicolas Delsuc and Clotilde Policar}, url = {https://www.hindawi.com/journals/omcl/2022/3858122/}, doi = {10.1155/2022/3858122}, issn = {1942-0900}, year = {2022}, date = {2022-01-01}, urldate = {2022-04-03}, journal = {Oxidative Medicine and Cellular Longevity}, volume = {2022}, pages = {e3858122}, abstract = {Oxidative stress is known to play a major role in the pathogenesis of inflammatory bowel diseases (IBDs), and, in particular, superoxide dismutase (SODs) defenses were shown to be weakened in patients suffering from IBDs. SOD mimics, also called SOD mimetics, as low-molecular-weight complexes reproducing the activity of SOD, constitute promising antioxidant catalytic metallodrugs in the context of IBDs. A Mn(II) complex SOD mimic (Mn1) based on an open-chain diaminoethane ligand exerting antioxidant and anti-inflammatory effects on an intestinal epithelial cellular model was shown to experience metal exchanges between the manganese center and metal ions present in the biological environment (such as Zn(II)) to some degrees. As the resulting complexes (mainly Zn(II)) were shown to be inactive, improving the kinetic inertness of Mn(II) complexes based on open-chain ligands is key to improve their bioactivity in a cellular context. We report here the study of three new Mn(II) complexes resulting from Mn1 functionalization with a cyclohexyl and/or a propyl group meant to limit, respectively, (a) metal exchanges and (b) deprotonation of an amine from the 1,2-diaminoethane central scaffold. The new manganese-based SOD mimics display a higher intrinsic SOD activity and also improved kinetic inertness in metal ion exchange processes (with Zn(II), Cu(II), Ni(II), and Co(II)). They were shown to provide anti-inflammatory and antioxidant effects in cells at lower doses than Mn1 (down to 10 μM). This improvement was due to their higher inertness against metal-assisted dissociation and not to different cellular overall accumulations. Based on its higher inertness, the SOD mimic containing both the propyl and the cyclohexyl moieties was suitable for intracellular detection and quantification by mass spectrometry, quantification, that was achieved by using a 13C-labeled Co-based analog of the SOD mimics as an external heavy standard.}, note = {Publisher: Hindawi}, keywords = {}, pubstate = {published}, tppubtype = {article} } Oxidative stress is known to play a major role in the pathogenesis of inflammatory bowel diseases (IBDs), and, in particular, superoxide dismutase (SODs) defenses were shown to be weakened in patients suffering from IBDs. SOD mimics, also called SOD mimetics, as low-molecular-weight complexes reproducing the activity of SOD, constitute promising antioxidant catalytic metallodrugs in the context of IBDs. A Mn(II) complex SOD mimic (Mn1) based on an open-chain diaminoethane ligand exerting antioxidant and anti-inflammatory effects on an intestinal epithelial cellular model was shown to experience metal exchanges between the manganese center and metal ions present in the biological environment (such as Zn(II)) to some degrees. As the resulting complexes (mainly Zn(II)) were shown to be inactive, improving the kinetic inertness of Mn(II) complexes based on open-chain ligands is key to improve their bioactivity in a cellular context. We report here the study of three new Mn(II) complexes resulting from Mn1 functionalization with a cyclohexyl and/or a propyl group meant to limit, respectively, (a) metal exchanges and (b) deprotonation of an amine from the 1,2-diaminoethane central scaffold. The new manganese-based SOD mimics display a higher intrinsic SOD activity and also improved kinetic inertness in metal ion exchange processes (with Zn(II), Cu(II), Ni(II), and Co(II)). They were shown to provide anti-inflammatory and antioxidant effects in cells at lower doses than Mn1 (down to 10 μM). This improvement was due to their higher inertness against metal-assisted dissociation and not to different cellular overall accumulations. Based on its higher inertness, the SOD mimic containing both the propyl and the cyclohexyl moieties was suitable for intracellular detection and quantification by mass spectrometry, quantification, that was achieved by using a 13C-labeled Co-based analog of the SOD mimics as an external heavy standard. |
SOD mimics: From the tool box of the chemists to cellular studies Article de journal Clotilde Policar; Jean Bouvet; Hélène C Bertrand; Nicolas Delsuc Current Opinion in Chemical Biology, 67 , p. 102109, 2022, ISSN: 1367-5931. @article{POLICAR2022102109, title = {SOD mimics: From the tool box of the chemists to cellular studies}, author = {Clotilde Policar and Jean Bouvet and H\'{e}l\`{e}ne C Bertrand and Nicolas Delsuc}, url = {https://www.sciencedirect.com/science/article/pii/S136759312100154X}, doi = {https://doi.org/10.1016/j.cbpa.2021.102109}, issn = {1367-5931}, year = {2022}, date = {2022-01-01}, journal = {Current Opinion in Chemical Biology}, volume = {67}, pages = {102109}, abstract = {Superoxide dismutases (SODs) are metalloproteins that protect cells against oxidative stress by controlling the concentration of superoxide (O2−) through catalysis of its dismutation. The activity of superoxide dismutases can be mimicked by low-molecular-weight complexes having potential therapeutic applications. This review presents recent strategies for designing efficient SOD mimics, from molecular metal complexes to nanomaterials. Studies of these systems in cells reveal that some SOD mimics, designed to react directly with superoxide, may also indirectly enhance the cellular antioxidant arsenal. Finally, a good understanding of the bioactivity requires information on the cell-penetration, speciation, and subcellular location of the SOD mimics: we will describe recent studies and new techniques that open opportunities for characterizing SOD mimics in biological environments.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Superoxide dismutases (SODs) are metalloproteins that protect cells against oxidative stress by controlling the concentration of superoxide (O2−) through catalysis of its dismutation. The activity of superoxide dismutases can be mimicked by low-molecular-weight complexes having potential therapeutic applications. This review presents recent strategies for designing efficient SOD mimics, from molecular metal complexes to nanomaterials. Studies of these systems in cells reveal that some SOD mimics, designed to react directly with superoxide, may also indirectly enhance the cellular antioxidant arsenal. Finally, a good understanding of the bioactivity requires information on the cell-penetration, speciation, and subcellular location of the SOD mimics: we will describe recent studies and new techniques that open opportunities for characterizing SOD mimics in biological environments. |
Cellular Detection of a Mitochondria Targeted Brominated Vinyl Triphenylamine Optical Probe (TP−Br) by X-Ray Fluorescence Microscopy Article de journal Sounderya Nagarajan; Florent Poyer; Laura Fourmois; Delphine Naud-Martin; Kadda Medjoubi; Andrea Somogyi; Gabrielle Schanne; Lucas Henry; Nicolas Delsuc; Clotilde Policar; Helene C Bertrand; Florence Mahuteau-Betzer Chemistry – A European Journal, 28 (15), p. e202104424, 2022. @article{https://doi.org/10.1002/chem.202104424, title = {Cellular Detection of a Mitochondria Targeted Brominated Vinyl Triphenylamine Optical Probe (TP−Br) by X-Ray Fluorescence Microscopy}, author = {Sounderya Nagarajan and Florent Poyer and Laura Fourmois and Delphine Naud-Martin and Kadda Medjoubi and Andrea Somogyi and Gabrielle Schanne and Lucas Henry and Nicolas Delsuc and Clotilde Policar and Helene C Bertrand and Florence Mahuteau-Betzer}, url = {https://chemistry-europe.onlinelibrary.wiley.com/doi/abs/10.1002/chem.202104424}, doi = {https://doi.org/10.1002/chem.202104424}, year = {2022}, date = {2022-01-01}, journal = {Chemistry \textendash A European Journal}, volume = {28}, number = {15}, pages = {e202104424}, abstract = {Abstract Triphenylamine (TP) derivatives such as two-branch cationic vinylbenzimidazolium triphenylamine TP−2Bzim are promising turn-on fluorescent probes suitable for two-photon imaging, labelling mitochondria in live cells. Here, we designed two TP−2Bzim derivatives as bimodal probes suitable for X-ray fluorescence imaging. The conjugation of the TP core with a rhenium tricarbonyl moiety in the TP−RePyta probe altered the localisation in live cells from mitochondria to lysosomes. The introduction of bromine on the TP core generated the TP−Br probe retaining good photophysical properties and mitochondria labelling in live cells. The influence of calcium channels in the uptake of TP−Br was studied. Synchrotron Radiation X-ray Fluorescence (SXRF) imaging of bromine enabled the detection of TP−Br and suggested a negligible presence of the probe in an unbound state in the incubated cells, a crucial point in the development of these probes. This study paves the way towards the development of TP probes as specific organelle stainers suitable for SXRF imaging.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Abstract Triphenylamine (TP) derivatives such as two-branch cationic vinylbenzimidazolium triphenylamine TP−2Bzim are promising turn-on fluorescent probes suitable for two-photon imaging, labelling mitochondria in live cells. Here, we designed two TP−2Bzim derivatives as bimodal probes suitable for X-ray fluorescence imaging. The conjugation of the TP core with a rhenium tricarbonyl moiety in the TP−RePyta probe altered the localisation in live cells from mitochondria to lysosomes. The introduction of bromine on the TP core generated the TP−Br probe retaining good photophysical properties and mitochondria labelling in live cells. The influence of calcium channels in the uptake of TP−Br was studied. Synchrotron Radiation X-ray Fluorescence (SXRF) imaging of bromine enabled the detection of TP−Br and suggested a negligible presence of the probe in an unbound state in the incubated cells, a crucial point in the development of these probes. This study paves the way towards the development of TP probes as specific organelle stainers suitable for SXRF imaging. |
Improvement of Peptidyl Copper Complexes Mimicking Catalase: A Subtle Balance between Thermodynamic Stability and Resistance towards H2O2 Degradation Article de journal Yaqine Ben Hadj Hammouda; Koudedja Coulibaly; Alimatou Bathily; Magdalene Teoh Sook Han; Clotilde Policar; Nicolas Delsuc Molecules, 27 (17), 2022, ISSN: 1420-3049. @article{molecules27175476, title = {Improvement of Peptidyl Copper Complexes Mimicking Catalase: A Subtle Balance between Thermodynamic Stability and Resistance towards H2O2 Degradation}, author = {Yaqine Ben Hadj Hammouda and Koudedja Coulibaly and Alimatou Bathily and Magdalene Teoh Sook Han and Clotilde Policar and Nicolas Delsuc}, url = {https://www.mdpi.com/1420-3049/27/17/5476}, doi = {10.3390/molecules27175476}, issn = {1420-3049}, year = {2022}, date = {2022-01-01}, journal = {Molecules}, volume = {27}, number = {17}, abstract = {Catalase mimics are low molecular weight metal complexes that reproduce the activity of catalase, an antioxidant metalloprotein that participates in the cellular regulation of H2O2 concentration by catalyzing its dismutation. H2O2 is a reactive oxygen species that is vital for the normal functioning of cells. However, its overproduction contributes to oxidative stress, which damages cells. Owing to their biocompatibility, peptidyl complexes are an attractive option for clinical applications to regulate H2O2 by enzyme mimics. We report here the synthesis and characterization of four new peptidyl di-copper complexes bearing two coordinating sequences. Characterization of the complexes showed that, depending on the linker used between the two coordinating sequences, their catalytic activity for H2O2 dismutation, their thermodynamic stability and their resistance to H2O2 degradation are very different, with (CATm2)Cu2 being the most promising catalyst.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Catalase mimics are low molecular weight metal complexes that reproduce the activity of catalase, an antioxidant metalloprotein that participates in the cellular regulation of H2O2 concentration by catalyzing its dismutation. H2O2 is a reactive oxygen species that is vital for the normal functioning of cells. However, its overproduction contributes to oxidative stress, which damages cells. Owing to their biocompatibility, peptidyl complexes are an attractive option for clinical applications to regulate H2O2 by enzyme mimics. We report here the synthesis and characterization of four new peptidyl di-copper complexes bearing two coordinating sequences. Characterization of the complexes showed that, depending on the linker used between the two coordinating sequences, their catalytic activity for H2O2 dismutation, their thermodynamic stability and their resistance to H2O2 degradation are very different, with (CATm2)Cu2 being the most promising catalyst. |
2021 |
A di-Copper Peptidyl Complex Mimics the Activity of Catalase, a Key Antioxidant Metalloenzyme Article de journal Koudedja Coulibaly; Marion Thauvin; Adyn Melenbacher; Clara Testard; Evangelina Trigoni; Amandine Vincent; Martin J Stillman; Sophie Vriz; Clotilde Policar; Nicolas Delsuc Inorganic Chemistry, 60 (13), p. 9309-9319, 2021. @article{doi:10.1021/acs.inorgchem.0c03718b, title = {A di-Copper Peptidyl Complex Mimics the Activity of Catalase, a Key Antioxidant Metalloenzyme}, author = {Koudedja Coulibaly and Marion Thauvin and Adyn Melenbacher and Clara Testard and Evangelina Trigoni and Amandine Vincent and Martin J Stillman and Sophie Vriz and Clotilde Policar and Nicolas Delsuc}, url = {https://doi.org/10.1021/acs.inorgchem.0c03718}, doi = {10.1021/acs.inorgchem.0c03718}, year = {2021}, date = {2021-01-01}, journal = {Inorganic Chemistry}, volume = {60}, number = {13}, pages = {9309-9319}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Rhenium carbonyl complexes bearing methylated triphenylphosphonium cations as antibody-free mitochondria trackers for X-ray fluorescence imaging Article de journal Gabrielle Schanne; Lucas Henry; How Chee Ong; Andrea Somogyi; Kadda Medjoubi; Nicolas Delsuc; Clotilde Policar; Felipe García; Helene C Bertrand Inorg. Chem. Front., 8 , p. 3905-3915, 2021. @article{D1QI00542A, title = {Rhenium carbonyl complexes bearing methylated triphenylphosphonium cations as antibody-free mitochondria trackers for X-ray fluorescence imaging}, author = {Gabrielle Schanne and Lucas Henry and How Chee Ong and Andrea Somogyi and Kadda Medjoubi and Nicolas Delsuc and Clotilde Policar and Felipe Garc\'{i}a and Helene C Bertrand}, url = {http://dx.doi.org/10.1039/D1QI00542A}, doi = {10.1039/D1QI00542A}, year = {2021}, date = {2021-01-01}, journal = {Inorg. Chem. Front.}, volume = {8}, pages = {3905-3915}, publisher = {The Royal Society of Chemistry}, abstract = {Synchrotron Radiation X-ray Fluorescence (SXRF) imaging is a powerful technique for the visualization of metal complexes in biological systems. However, due to the lack of an endogenous elemental signature for mitochondria, probes for the localization of this organelle are required for colocalization studies. In this work, we designed and synthesized rhenium pyta tricarbonyl complexes conjugated to methylated triphenylphosphonium TP*P+ cations as multimodal probes for the visualization of mitochondria, suitable for fluorescence and SXRF imaging and quantification. Accumulation of the methylated triphenylphosphonium TP*P+-based conjugates in cells was observed in fixed A549 cells, and the amount of mitochondrial uptake was linked to the lipophilicity of the TPP+ vector. Our work highlights a convenient rhenium-based multimodal mitochondrial-targeted probe compatible with SXRF nano-imaging.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Synchrotron Radiation X-ray Fluorescence (SXRF) imaging is a powerful technique for the visualization of metal complexes in biological systems. However, due to the lack of an endogenous elemental signature for mitochondria, probes for the localization of this organelle are required for colocalization studies. In this work, we designed and synthesized rhenium pyta tricarbonyl complexes conjugated to methylated triphenylphosphonium TP*P+ cations as multimodal probes for the visualization of mitochondria, suitable for fluorescence and SXRF imaging and quantification. Accumulation of the methylated triphenylphosphonium TP*P+-based conjugates in cells was observed in fixed A549 cells, and the amount of mitochondrial uptake was linked to the lipophilicity of the TPP+ vector. Our work highlights a convenient rhenium-based multimodal mitochondrial-targeted probe compatible with SXRF nano-imaging. |
Evaluation of the compounds commonly known as superoxide dismutase and catalase mimics in cellular models Article de journal Amandine Vincent; Marion Thauvin; Elodie Quévrain; Emilie Mathieu; Sarah Layani; Philippe Seksik; Ines Batinic-Haberle; Sophie Vriz; Clotilde Policar; Nicolas Delsuc Journal of Inorganic Biochemistry, p. 111431, 2021, ISSN: 0162-0134. @article{VINCENT2021111431, title = {Evaluation of the compounds commonly known as superoxide dismutase and catalase mimics in cellular models}, author = {Amandine Vincent and Marion Thauvin and Elodie Qu\'{e}vrain and Emilie Mathieu and Sarah Layani and Philippe Seksik and Ines Batinic-Haberle and Sophie Vriz and Clotilde Policar and Nicolas Delsuc}, url = {https://www.sciencedirect.com/science/article/pii/S0162013421000787}, doi = {https://doi.org/10.1016/j.jinorgbio.2021.111431}, issn = {0162-0134}, year = {2021}, date = {2021-01-01}, journal = {Journal of Inorganic Biochemistry}, pages = {111431}, abstract = {Oxidative stress that results from an imbalance between the concentrations of reactive species (RS) and antioxidant defenses is associated with many pathologies. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase are among the key enzymes that maintain the low nanomolar physiological concentrations of superoxide and hydrogen peroxide. The increase in the levels of these species and their progeny could have deleterious effects. In this context, chemists have developed SOD and CAT mimics to supplement them when cells are overwhelmed with oxidative stress. However, the beneficial activity of such molecules in cells depends not only on their intrinsic catalytic activities but also on their stability in biological context, their cell penetration and their cellular localization. We have employed cellular assays to characterize several compounds that possess SOD and CAT activities and have been frequently used in cellular and animal models. We used cellular assays that address SOD and CAT activities of the compounds. Finally, we determined the effect of compounds on the suppression of the inflammation in HT29-MD2 cells challenged by lipopolysaccharide. When the assay requires penetration inside cells, the SOD mimics Mn(III) meso-tetrakis(N-(2′-nbutoxyethyl)pyridinium-2-yl)porphyrin (MnTnBuOE-2-PyP5+) and Mn(II) dichloro[(4aR,13aR,17aR,21aR)-1,2,3,4,4a,5, 6,12,13,13a,14,15,16,17,17a,18,19,20,21,21a-eicosahydro-11,7-nitrilo-7Hdibenzo[b,h] [1, 4, 7, 10] tetra--azacycloheptadecine-κN5,κN13,κN18,κN21,κN22] (Imisopasem manganese, M40403, CG4419) were found efficacious at 10 μM, while Mn(II) chloro N-(phenolato)-N,N′-bis[2-(N-methyl-imidazolyl)methyl]-ethane-1,2-diamine (Mn1) requires an incubation at 100 μM. This study thus demonstrates that MnTnBuOE-2-PyP5+, M40403 and Mn1 were efficacious in suppressing inflammatory response in HT29-MD2 cells and such action appears to be related to their ability to enter the cells and modulate reactive oxygen species (ROS) levels.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Oxidative stress that results from an imbalance between the concentrations of reactive species (RS) and antioxidant defenses is associated with many pathologies. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase are among the key enzymes that maintain the low nanomolar physiological concentrations of superoxide and hydrogen peroxide. The increase in the levels of these species and their progeny could have deleterious effects. In this context, chemists have developed SOD and CAT mimics to supplement them when cells are overwhelmed with oxidative stress. However, the beneficial activity of such molecules in cells depends not only on their intrinsic catalytic activities but also on their stability in biological context, their cell penetration and their cellular localization. We have employed cellular assays to characterize several compounds that possess SOD and CAT activities and have been frequently used in cellular and animal models. We used cellular assays that address SOD and CAT activities of the compounds. Finally, we determined the effect of compounds on the suppression of the inflammation in HT29-MD2 cells challenged by lipopolysaccharide. When the assay requires penetration inside cells, the SOD mimics Mn(III) meso-tetrakis(N-(2′-nbutoxyethyl)pyridinium-2-yl)porphyrin (MnTnBuOE-2-PyP5+) and Mn(II) dichloro[(4aR,13aR,17aR,21aR)-1,2,3,4,4a,5, 6,12,13,13a,14,15,16,17,17a,18,19,20,21,21a-eicosahydro-11,7-nitrilo-7Hdibenzo[b,h] [1, 4, 7, 10] tetra--azacycloheptadecine-κN5,κN13,κN18,κN21,κN22] (Imisopasem manganese, M40403, CG4419) were found efficacious at 10 μM, while Mn(II) chloro N-(phenolato)-N,N′-bis[2-(N-methyl-imidazolyl)methyl]-ethane-1,2-diamine (Mn1) requires an incubation at 100 μM. This study thus demonstrates that MnTnBuOE-2-PyP5+, M40403 and Mn1 were efficacious in suppressing inflammatory response in HT29-MD2 cells and such action appears to be related to their ability to enter the cells and modulate reactive oxygen species (ROS) levels. |
2020 |
Recent Emergence of Rhenium(I) Tricarbonyl Complexes as Photosensitisers for Cancer Therapy Article de journal Hui Shan Liew; Chun-Wai Mai; Mohd Zulkefeli; Thiagarajan Madheswaran; Lik Voon Kiew; Nicolas Delsuc; May Lee Low Molecules, 25 (18), 2020, ISSN: 1420-3049. @article{molecules25184176, title = {Recent Emergence of Rhenium(I) Tricarbonyl Complexes as Photosensitisers for Cancer Therapy}, author = {Hui Shan Liew and Chun-Wai Mai and Mohd Zulkefeli and Thiagarajan Madheswaran and Lik Voon Kiew and Nicolas Delsuc and May Lee Low}, url = {https://www.mdpi.com/1420-3049/25/18/4176}, doi = {10.3390/molecules25184176}, issn = {1420-3049}, year = {2020}, date = {2020-01-01}, journal = {Molecules}, volume = {25}, number = {18}, abstract = {Photodynamic therapy (PDT) is emerging as a significant complementary or alternative approach for cancer treatment. PDT drugs act as photosensitisers, which upon using appropriate wavelength light and in the presence of molecular oxygen, can lead to cell death. Herein, we reviewed the general characteristics of the different generation of photosensitisers. We also outlined the emergence of rhenium (Re) and more specifically, Re(I) tricarbonyl complexes as a new generation of metal-based photosensitisers for photodynamic therapy that are of great interest in multidisciplinary research. The photophysical properties and structures of Re(I) complexes discussed in this review are summarised to determine basic features and similarities among the structures that are important for their phototoxic activity and future investigations. We further examined the in vitro and in vivo efficacies of the Re(I) complexes that have been synthesised for anticancer purposes. We also discussed Re(I) complexes in conjunction with the advancement of two-photon PDT, drug combination study, nanomedicine, and photothermal therapy to overcome the limitation of such complexes, which generally absorb short wavelengths.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Photodynamic therapy (PDT) is emerging as a significant complementary or alternative approach for cancer treatment. PDT drugs act as photosensitisers, which upon using appropriate wavelength light and in the presence of molecular oxygen, can lead to cell death. Herein, we reviewed the general characteristics of the different generation of photosensitisers. We also outlined the emergence of rhenium (Re) and more specifically, Re(I) tricarbonyl complexes as a new generation of metal-based photosensitisers for photodynamic therapy that are of great interest in multidisciplinary research. The photophysical properties and structures of Re(I) complexes discussed in this review are summarised to determine basic features and similarities among the structures that are important for their phototoxic activity and future investigations. We further examined the in vitro and in vivo efficacies of the Re(I) complexes that have been synthesised for anticancer purposes. We also discussed Re(I) complexes in conjunction with the advancement of two-photon PDT, drug combination study, nanomedicine, and photothermal therapy to overcome the limitation of such complexes, which generally absorb short wavelengths. |
Differentiation of neural-type cells on multi-scale ordered collagen-silica bionanocomposites Article de journal Nicolas Debons; Dounia Dems; Christophe Hélary; Sylvain Le Grill; Lise Picaut; Flore Renaud; Nicolas Delsuc; Marie-Claire Schanne-Klein; Thibaud Coradin; Carole Aimé Biomater. Sci., 8 , p. 569-576, 2020. @article{C9BM01029Gb, title = {Differentiation of neural-type cells on multi-scale ordered collagen-silica bionanocomposites}, author = {Nicolas Debons and Dounia Dems and Christophe H\'{e}lary and Sylvain Le Grill and Lise Picaut and Flore Renaud and Nicolas Delsuc and Marie-Claire Schanne-Klein and Thibaud Coradin and Carole Aim\'{e}}, url = {http://dx.doi.org/10.1039/C9BM01029G}, doi = {10.1039/C9BM01029G}, year = {2020}, date = {2020-01-01}, journal = {Biomater. Sci.}, volume = {8}, pages = {569-576}, publisher = {The Royal Society of Chemistry}, abstract = {Cells respond to biophysical and biochemical signals. We developed a composite filament from collagen and silica particles modified to interact with collagen and/or present a laminin epitope (IKVAV) crucial for cell\textendashmatrix adhesion and signal transduction. This combines scaffolding and signaling and shows that local tuning of collagen organization enhances cell differentiation.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Cells respond to biophysical and biochemical signals. We developed a composite filament from collagen and silica particles modified to interact with collagen and/or present a laminin epitope (IKVAV) crucial for cell–matrix adhesion and signal transduction. This combines scaffolding and signaling and shows that local tuning of collagen organization enhances cell differentiation. |
Anti-inflammatory activity of superoxide dismutase mimics functionalized with cell-penetrating peptides Article de journal Emilie Mathieu; Anne-Sophie Bernard; Vincent H Y Ching; Andrea Somogyi; Kadda Medjoubi; Jennifer Rodon Fores; Hélène C Bertrand; Amandine Vincent; Sylvain Trépout; Jean-Luc Guerquin-Kern; Andreas Scheitler; Ivana Ivanović-Burmazović; Philippe Seksik; Nicolas Delsuc; Clotilde Policar Dalton Trans., 49 , p. 2323-2330, 2020. @article{C9DT04619Db, title = {Anti-inflammatory activity of superoxide dismutase mimics functionalized with cell-penetrating peptides}, author = {Emilie Mathieu and Anne-Sophie Bernard and Vincent H Y Ching and Andrea Somogyi and Kadda Medjoubi and Jennifer Rodon Fores and H\'{e}l\`{e}ne C Bertrand and Amandine Vincent and Sylvain Tr\'{e}pout and Jean-Luc Guerquin-Kern and Andreas Scheitler and Ivana Ivanovi\'{c}-Burmazovi\'{c} and Philippe Seksik and Nicolas Delsuc and Clotilde Policar}, url = {http://dx.doi.org/10.1039/C9DT04619D}, doi = {10.1039/C9DT04619D}, year = {2020}, date = {2020-01-01}, journal = {Dalton Trans.}, volume = {49}, pages = {2323-2330}, publisher = {The Royal Society of Chemistry}, abstract = {A superoxide dismutase mimic (Mn1) was functionalized with three positively charged-peptides: RRRRRRRRR (Mn1-R9), RRWWWRRWRR (Mn1-RW9) or Fx-r-Fx-K (Mn1-MPP). Characterization of the physico-chemical properties of the complexes show that they share similar binding affinity for Mn2+, apparent reduction potential and intrinsic superoxide dismutase activity. However, their accumulation in cells is different (Mn1-R9 < Mn1-MPP < Mn1-RW9 < Mn1), as well as their subcellular distribution. In addition, the three functionalized-complexes display a better anti-inflammatory activity than Mn1 when assayed at 10 μM. This improvement is due to a combination of an anti-inflammatory effect of the peptidyl moiety itself, and of the SOD mimic for Mn1-RW9 and Mn1-MPP. In contrast, the enhanced anti-inflammatory activity of Mn1-R9 is solely due to the SOD mimic.}, keywords = {}, pubstate = {published}, tppubtype = {article} } A superoxide dismutase mimic (Mn1) was functionalized with three positively charged-peptides: RRRRRRRRR (Mn1-R9), RRWWWRRWRR (Mn1-RW9) or Fx-r-Fx-K (Mn1-MPP). Characterization of the physico-chemical properties of the complexes show that they share similar binding affinity for Mn2+, apparent reduction potential and intrinsic superoxide dismutase activity. However, their accumulation in cells is different (Mn1-R9 < Mn1-MPP < Mn1-RW9 < Mn1), as well as their subcellular distribution. In addition, the three functionalized-complexes display a better anti-inflammatory activity than Mn1 when assayed at 10 μM. This improvement is due to a combination of an anti-inflammatory effect of the peptidyl moiety itself, and of the SOD mimic for Mn1-RW9 and Mn1-MPP. In contrast, the enhanced anti-inflammatory activity of Mn1-R9 is solely due to the SOD mimic. |
Intracellular location matters: rationalization of the anti-inflammatory activity of a manganese(ii) superoxide dismutase mimic complex Article de journal Emilie Mathieu; Anne-Sophie Bernard; Elodie Quévrain; Martha Zoumpoulaki; Sébastien Iriart; Caroline Lung-Soong; Barry Lai; Kadda Medjoubi; Lucas Henry; Sounderya Nagarajan; Florent Poyer; Andreas Scheitler; Ivana Ivanović-Burmazović; Sergio Marco; Andrea Somogyi; Philippe Seksik; Nicolas Delsuc; Clotilde Policar Chem. Commun., p. -, 2020. @article{D0CC03398G, title = {Intracellular location matters: rationalization of the anti-inflammatory activity of a manganese(ii) superoxide dismutase mimic complex}, author = {Emilie Mathieu and Anne-Sophie Bernard and Elodie Qu\'{e}vrain and Martha Zoumpoulaki and S\'{e}bastien Iriart and Caroline Lung-Soong and Barry Lai and Kadda Medjoubi and Lucas Henry and Sounderya Nagarajan and Florent Poyer and Andreas Scheitler and Ivana Ivanovi\'{c}-Burmazovi\'{c} and Sergio Marco and Andrea Somogyi and Philippe Seksik and Nicolas Delsuc and Clotilde Policar}, url = {http://dx.doi.org/10.1039/D0CC03398G}, doi = {10.1039/D0CC03398G}, year = {2020}, date = {2020-01-01}, journal = {Chem. Commun.}, pages = {-}, publisher = {The Royal Society of Chemistry}, abstract = {A conjugate of a Mn-based superoxide dismutase mimic with a Re-based multimodal probe ̲ was studied in a cellular model of oxidative stress. Its speciation was investigated using Re and Mn X-fluorescence. Interestingly, ̲ shows a distribution different from its unconjugated analogue but a similar concentration in mitochondria and a similar bioactivity.}, keywords = {}, pubstate = {published}, tppubtype = {article} } A conjugate of a Mn-based superoxide dismutase mimic with a Re-based multimodal probe ̲ was studied in a cellular model of oxidative stress. Its speciation was investigated using Re and Mn X-fluorescence. Interestingly, ̲ shows a distribution different from its unconjugated analogue but a similar concentration in mitochondria and a similar bioactivity. |
An easy-to-implement combinatorial approach involving an activity-based assay for the discovery of a peptidyl copper complex mimicking superoxide dismutase Article de journal Amandine Vincent; Jennifer Rodon Fores; Elodie Tauziet; Elodie Quévrain; Ágnes Dancs; Amandine Conte-Daban; Anne-Sophie Bernard; Philippe Pelupessy; Koudedja Coulibaly; Philippe Seksik; Christelle Hureau; Katalin Selmeczi; Clotilde Policar; Nicolas Delsuc Chem. Commun., 56 , p. 399-402, 2020. @article{C9CC07920C, title = {An easy-to-implement combinatorial approach involving an activity-based assay for the discovery of a peptidyl copper complex mimicking superoxide dismutase}, author = {Amandine Vincent and Jennifer Rodon Fores and Elodie Tauziet and Elodie Qu\'{e}vrain and \'{A}gnes Dancs and Amandine Conte-Daban and Anne-Sophie Bernard and Philippe Pelupessy and Koudedja Coulibaly and Philippe Seksik and Christelle Hureau and Katalin Selmeczi and Clotilde Policar and Nicolas Delsuc}, url = {http://dx.doi.org/10.1039/C9CC07920C}, doi = {10.1039/C9CC07920C}, year = {2020}, date = {2020-01-01}, journal = {Chem. Commun.}, volume = {56}, pages = {399-402}, publisher = {The Royal Society of Chemistry}, abstract = {A combinatorial approach using a one-bead-one-compound method and a screening based on a SOD-activity assay was set up for the discovery of an efficient peptidyl copper complex. The complex exhibited good stability constants, suitable redox potentials and excellent intrinsic activity. This complex was further assayed in cells for its antioxidant properties and showed beneficial effects when cells were subjected to oxidative stress.}, keywords = {}, pubstate = {published}, tppubtype = {article} } A combinatorial approach using a one-bead-one-compound method and a screening based on a SOD-activity assay was set up for the discovery of an efficient peptidyl copper complex. The complex exhibited good stability constants, suitable redox potentials and excellent intrinsic activity. This complex was further assayed in cells for its antioxidant properties and showed beneficial effects when cells were subjected to oxidative stress. |
2018 |
Labeling of Hyaluronic Acids with a Rhenium-tricarbonyl Tag and Percutaneous Penetration Studied by Multimodal Imaging Article de journal L Henry; N Delsuc; C Laugel; F Lambert; C Sandt; S Hostachy; A -S Bernard; H C Bertrand; L Grimaud; A Baillet-Guffroy; C Policar Bioconjugate Chemistry, 29 (4), p. 987–991, 2018. @article{Henry:2018, title = {Labeling of Hyaluronic Acids with a Rhenium-tricarbonyl Tag and Percutaneous Penetration Studied by Multimodal Imaging}, author = {L Henry and N Delsuc and C Laugel and F Lambert and C Sandt and S Hostachy and A -S Bernard and H C Bertrand and L Grimaud and A Baillet-Guffroy and C Policar}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85045549363&doi=10.1021%2facs.bioconjchem.7b00825&partnerID=40&md5=87140714a264358836c5f4c7734e49a3}, doi = {10.1021/acs.bioconjchem.7b00825}, year = {2018}, date = {2018-01-01}, journal = {Bioconjugate Chemistry}, volume = {29}, number = {4}, pages = {987--991}, abstract = {Hyaluronic acids were labeled with a rhenium-tricarbonyl used as single core multimodal probe for imaging and their penetration into human skin biopsies was studied using IR microscopy and fluorescence imaging (labeled SCoMPI). The penetration was shown to be dependent on the molecular weight of the molecule and limited to the upper layer of the skin. © 2018 American Chemical Society.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Hyaluronic acids were labeled with a rhenium-tricarbonyl used as single core multimodal probe for imaging and their penetration into human skin biopsies was studied using IR microscopy and fluorescence imaging (labeled SCoMPI). The penetration was shown to be dependent on the molecular weight of the molecule and limited to the upper layer of the skin. © 2018 American Chemical Society. |
Graftable SCoMPIs enable the labeling and X-ray fluorescence imaging of proteins Article de journal S Hostachy; M Masuda; T Miki; I Hamachi; S Sagan; O Lequin; K Medjoubi; A Somogyi; N Delsuc; C Policar Chemical Science, 9 (19), p. 4483–4487, 2018. @article{Hostachy:2018, title = {Graftable SCoMPIs enable the labeling and X-ray fluorescence imaging of proteins}, author = {S Hostachy and M Masuda and T Miki and I Hamachi and S Sagan and O Lequin and K Medjoubi and A Somogyi and N Delsuc and C Policar}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85047244059&doi=10.1039%2fc8sc00886h&partnerID=40&md5=4625eaa891ccc665a2357b73e20e3541}, doi = {10.1039/c8sc00886h}, year = {2018}, date = {2018-01-01}, journal = {Chemical Science}, volume = {9}, number = {19}, pages = {4483--4487}, abstract = {Bio-imaging techniques alternative to fluorescence microscopy are gaining increasing interest as complementary tools to visualize and analyze biological systems. Among them, X-ray fluorescence microspectroscopy provides information on the local content and distribution of heavy elements (Z ≥ 14) in cells or biological samples. In this context, similar tools to those developed for fluorescence microscopy are desired, including chemical probes or tags. In this work, we study rhenium complexes as a convenient and sensitive probe for X-ray fluorescence microspectroscopy. We demonstrate their ability to label and sense exogenously incubated or endogenous proteins inside cells. © The Royal Society of Chemistry 2018.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Bio-imaging techniques alternative to fluorescence microscopy are gaining increasing interest as complementary tools to visualize and analyze biological systems. Among them, X-ray fluorescence microspectroscopy provides information on the local content and distribution of heavy elements (Z ≥ 14) in cells or biological samples. In this context, similar tools to those developed for fluorescence microscopy are desired, including chemical probes or tags. In this work, we study rhenium complexes as a convenient and sensitive probe for X-ray fluorescence microspectroscopy. We demonstrate their ability to label and sense exogenously incubated or endogenous proteins inside cells. © The Royal Society of Chemistry 2018. |
A Metallo Pro-Drug to Target CuII in the Context of Alzheimer's Disease Article de journal A Conte-Daban; V Ambike; R Guillot; N Delsuc; C Policar; C Hureau Chemistry - A European Journal, 24 (20), p. 5095–5099, 2018. @article{Conte-Daban:2018, title = {A Metallo Pro-Drug to Target CuII in the Context of Alzheimer's Disease}, author = {A Conte-Daban and V Ambike and R Guillot and N Delsuc and C Policar and C Hureau}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85045131927&doi=10.1002%2fchem.201706049&partnerID=40&md5=5dc310a9e12535e296ba5429250159d3}, doi = {10.1002/chem.201706049}, year = {2018}, date = {2018-01-01}, journal = {Chemistry - A European Journal}, volume = {24}, number = {20}, pages = {5095--5099}, abstract = {Alzheimer's disease and oxidative stress are connected. In the present communication, we report the use of a MnII-based superoxide dismutase (SOD) mimic ([MnII(L)]+, 1+) as a pro-drug candidate to target CuII-associated events, namely, CuII-induced formation of reactive oxygen species (ROS) and modulation of the amyloid-β (Aβ) peptide aggregation. Complex 1+ is able to remove CuII from Aβ, stop ROS and prevent alteration of Aβ aggregation as would do the corresponding free ligand LH. Using 1+ instead of LH in further biological applications would have the double advantage to avoid the cell toxicity of LH and to benefit from its proved SOD-like activity. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim}, keywords = {}, pubstate = {published}, tppubtype = {article} } Alzheimer's disease and oxidative stress are connected. In the present communication, we report the use of a MnII-based superoxide dismutase (SOD) mimic ([MnII(L)]+, 1+) as a pro-drug candidate to target CuII-associated events, namely, CuII-induced formation of reactive oxygen species (ROS) and modulation of the amyloid-β (Aβ) peptide aggregation. Complex 1+ is able to remove CuII from Aβ, stop ROS and prevent alteration of Aβ aggregation as would do the corresponding free ligand LH. Using 1+ instead of LH in further biological applications would have the double advantage to avoid the cell toxicity of LH and to benefit from its proved SOD-like activity. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim |
2017 |
Re(I) carbonyl complexes: Multimodal platforms for inorganic chemical biology Article de journal S Hostachy; C Policar; N Delsuc Coordination Chemistry Reviews, 351 , p. 172–188, 2017. @article{Hostachy:2017, title = {Re(I) carbonyl complexes: Multimodal platforms for inorganic chemical biology}, author = {S Hostachy and C Policar and N Delsuc}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85020033654&doi=10.1016%2fj.ccr.2017.05.004&partnerID=40&md5=ea1241c6f9199448b3fbb2bfc259b363}, doi = {10.1016/j.ccr.2017.05.004}, year = {2017}, date = {2017-01-01}, journal = {Coordination Chemistry Reviews}, volume = {351}, pages = {172--188}, abstract = {Bio-imaging, by enabling the visualization of biomolecules of interest, has proved to be highly informative in the study of biological processes. Although fluorescence microscopy is probably one of the most used techniques, alternative methods of imaging, providing complementary information, are emerging. In this context, metal complexes represent valuable platforms for multimodal imaging, since they may combine interesting spectroscopic features and biologically relevant functionalization on a single molecular core. In particular, d6 low-spin rhenium tri-carbonyl complexes display unique luminescence and vibrational properties, and can be readily functionalized. Here we review their applications and potential as probes or drugs relying on their photophysical properties, before focusing on their use as multimodal probes for the labelling and imaging of peptides and proteins. © 2017 Elsevier B.V.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Bio-imaging, by enabling the visualization of biomolecules of interest, has proved to be highly informative in the study of biological processes. Although fluorescence microscopy is probably one of the most used techniques, alternative methods of imaging, providing complementary information, are emerging. In this context, metal complexes represent valuable platforms for multimodal imaging, since they may combine interesting spectroscopic features and biologically relevant functionalization on a single molecular core. In particular, d6 low-spin rhenium tri-carbonyl complexes display unique luminescence and vibrational properties, and can be readily functionalized. Here we review their applications and potential as probes or drugs relying on their photophysical properties, before focusing on their use as multimodal probes for the labelling and imaging of peptides and proteins. © 2017 Elsevier B.V. |
E Mathieu; A -S Bernard; N Delsuc; E Quévrain; G Gazzah; B Lai; F Chain; P Langella; M Bachelet; J Masliah; P Seksik; C Policar Inorganic Chemistry, 56 (5), p. 2545–2555, 2017. @article{Mathieu:2017, title = {A Cell-Penetrant Manganese Superoxide Dismutase (MnSOD) Mimic Is Able to Complement MnSOD and Exerts an Antiinflammatory Effect on Cellular and Animal Models of Inflammatory Bowel Diseases}, author = {E Mathieu and A -S Bernard and N Delsuc and E Qu\'{e}vrain and G Gazzah and B Lai and F Chain and P Langella and M Bachelet and J Masliah and P Seksik and C Policar}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85014763334&doi=10.1021%2facs.inorgchem.6b02695&partnerID=40&md5=acd51065ea36d5da707ec8c1915634a0}, doi = {10.1021/acs.inorgchem.6b02695}, year = {2017}, date = {2017-01-01}, journal = {Inorganic Chemistry}, volume = {56}, number = {5}, pages = {2545--2555}, abstract = {Inorganic complexes are increasingly used for biological and medicinal applications, and the question of the cell penetration and distribution of metallodrugs is key to understanding their biological activity. Oxidative stress is known to be involved in inflammation and in inflammatory bowel diseases for which antioxidative defenses are weakened. We report here the study of the manganese complex Mn1 mimicking superoxide dismutase (SOD), a protein involved in cell protection against oxidative stress, using an approach in inorganic cellular chemistry combining the investigation of Mn1 intracellular speciation using mass spectrometry and of its quantification and distribution using electron paramagnetic resonance and spatially resolved X-ray fluorescence with evaluation of its biological activity. More precisely, we have looked for and found the MS signature of Mn1 in cell lysates and quantified the overall manganese content. Intestinal epithelial cells activated by bacterial lipopolysaccharide were taken as a cellular model of oxidative stress and inflammation. DNBS-induced colitis in mice was used to investigate Mn1 activity in vivo. Mn1 exerts an intracellular antiinflammatory activity, remains at least partially coordinated, with diffuse distribution over the whole cell, and functionally complements mitochondrial MnSOD. © 2017 American Chemical Society.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Inorganic complexes are increasingly used for biological and medicinal applications, and the question of the cell penetration and distribution of metallodrugs is key to understanding their biological activity. Oxidative stress is known to be involved in inflammation and in inflammatory bowel diseases for which antioxidative defenses are weakened. We report here the study of the manganese complex Mn1 mimicking superoxide dismutase (SOD), a protein involved in cell protection against oxidative stress, using an approach in inorganic cellular chemistry combining the investigation of Mn1 intracellular speciation using mass spectrometry and of its quantification and distribution using electron paramagnetic resonance and spatially resolved X-ray fluorescence with evaluation of its biological activity. More precisely, we have looked for and found the MS signature of Mn1 in cell lysates and quantified the overall manganese content. Intestinal epithelial cells activated by bacterial lipopolysaccharide were taken as a cellular model of oxidative stress and inflammation. DNBS-induced colitis in mice was used to investigate Mn1 activity in vivo. Mn1 exerts an intracellular antiinflammatory activity, remains at least partially coordinated, with diffuse distribution over the whole cell, and functionally complements mitochondrial MnSOD. © 2017 American Chemical Society. |
A host-guest system based on collagen-like triple-helix hybridization Article de journal N Delsuc; S Uchinomiya; A Ojida; I Hamachi Chemical Communications, 53 (51), p. 6856–6859, 2017. @article{Delsuc:2017, title = {A host-guest system based on collagen-like triple-helix hybridization}, author = {N Delsuc and S Uchinomiya and A Ojida and I Hamachi}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85021764142&doi=10.1039%2fc7cc03055j&partnerID=40&md5=702ef29356b9c2adcdde22eeaaafb981}, doi = {10.1039/c7cc03055j}, year = {2017}, date = {2017-01-01}, journal = {Chemical Communications}, volume = {53}, number = {51}, pages = {6856--6859}, abstract = {A strategy inspired by tweezer receptors has been employed to develop a new host-guest system. The hybridization into a collagen-like triple helix is the driving force for the recognition that occurs with high affinity and selectivity. Several systems have been screened to find the best host-guest pair and this strategy may be implemented for tag fused protein recognition. © 2017 The Royal Society of Chemistry.}, keywords = {}, pubstate = {published}, tppubtype = {article} } A strategy inspired by tweezer receptors has been employed to develop a new host-guest system. The hybridization into a collagen-like triple helix is the driving force for the recognition that occurs with high affinity and selectivity. Several systems have been screened to find the best host-guest pair and this strategy may be implemented for tag fused protein recognition. © 2017 The Royal Society of Chemistry. |