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  1. AU="Gilles Subra"
  2. AU="Potocnik, Ana"
  3. AU="Butt, Christine"

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  1. Artikel ; Online: A Collagen-Mimetic Organic-Inorganic Hydrogel for Cartilage Engineering

    Laurine Valot / Marie Maumus / Luc Brunel / Jean Martinez / Muriel Amblard / Danièle Noël / Ahmad Mehdi / Gilles Subra

    Gels, Vol 7, Iss 73, p

    2021  Band 73

    Abstract: Promising strategies for cartilage regeneration rely on the encapsulation of mesenchymal stromal cells (MSCs) in a hydrogel followed by an injection into the injured joint. Preclinical and clinical data using MSCs embedded in a collagen gel have ... ...

    Abstract Promising strategies for cartilage regeneration rely on the encapsulation of mesenchymal stromal cells (MSCs) in a hydrogel followed by an injection into the injured joint. Preclinical and clinical data using MSCs embedded in a collagen gel have demonstrated improvements in patients with focal lesions and osteoarthritis. However, an improvement is often observed in the short or medium term due to the loss of the chondrocyte capacity to produce the correct extracellular matrix and to respond to mechanical stimulation. Developing novel biomimetic materials with better chondroconductive and mechanical properties is still a challenge for cartilage engineering. Herein, we have designed a biomimetic chemical hydrogel based on silylated collagen-mimetic synthetic peptides having the ability to encapsulate MSCs using a biorthogonal sol-gel cross-linking reaction. By tuning the hydrogel composition using both mono- and bi-functional peptides, we succeeded in improving its mechanical properties, yielding a more elastic scaffold and achieving the survival of embedded MSCs for 21 days as well as the up-regulation of chondrocyte markers. This biomimetic long-standing hybrid hydrogel is of interest as a synthetic and modular scaffold for cartilage tissue engineering.
    Schlagwörter hydrogel ; sol-gel ; hybrid material ; collagen-mimetic peptide ; cartilage tissue engineering ; mesenchymal stromal cells ; Science ; Q ; Chemistry ; QD1-999 ; Inorganic chemistry ; QD146-197 ; General. Including alchemy ; QD1-65
    Thema/Rubrik (Code) 620
    Sprache Englisch
    Erscheinungsdatum 2021-06-01T00:00:00Z
    Verlag MDPI AG
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  2. Artikel ; Online: Inorganic Sol–Gel Polymerization for Hydrogel Bioprinting

    Titouan Montheil / Marie Maumus / Laurine Valot / Aurélien Lebrun / Jean Martinez / Muriel Amblard / Danièle Noël / Ahmad Mehdi / Gilles Subra

    ACS Omega, Vol 5, Iss 6, Pp 2640-

    2020  Band 2647

    Schlagwörter Chemistry ; QD1-999
    Sprache Englisch
    Erscheinungsdatum 2020-02-01T00:00:00Z
    Verlag American Chemical Society
    Dokumenttyp Artikel ; Online
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  3. Artikel: Inorganic polymerization: an attractive route to biocompatible hybrid hydrogels

    Montheil, Titouan / Cécile Echalier / Jean Martinez / Gilles Subra / Ahmad Mehdi

    Journal of materials chemistry. 2018 May 30, v. 6, no. 21

    2018  

    Abstract: As an intermediate state between liquid and solid materials, hydrogels display unique properties, opening a wide scope of applications, especially in the biomedical field. Organic hydrogels are composed of an organic network cross-linked via chemical or ... ...

    Abstract As an intermediate state between liquid and solid materials, hydrogels display unique properties, opening a wide scope of applications, especially in the biomedical field. Organic hydrogels are composed of an organic network cross-linked via chemical or physical reticulation nodes. In contrast, hybrid hydrogels are defined by the coexistence of organic and inorganic moieties in water. Inorganic polymerization, i.e. the sol–gel process, is one of the main techniques leading to hybrid hydrogels. The chemoselectivity of this method proceeds through hydrolysis and condensation reactions of metal oxide moieties. In addition, the mild reaction conditions make this process very promising for the preparation of water-containing materials and their bio-applications.
    Schlagwörter chemoselectivity ; condensation reactions ; crosslinking ; hydrogels ; hydrolysis ; liquids ; moieties ; polymerization ; sol-gel processing
    Sprache Englisch
    Erscheinungsverlauf 2018-0530
    Umfang p. 3434-3448.
    Erscheinungsort The Royal Society of Chemistry
    Dokumenttyp Artikel
    ZDB-ID 2702241-9
    ISSN 2050-7518 ; 2050-750X
    ISSN (online) 2050-7518
    ISSN 2050-750X
    DOI 10.1039/c8tb00456k
    Datenquelle NAL Katalog (AGRICOLA)

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  4. Artikel ; Online: Development of Amino Acids Functionalized SBA-15 for the Improvement of Protein Adsorption

    Raquel Gutiérrez-Climente / Margaux Clavié / Jérémie Gouyon / Giang Ngo / Yoann Ladner / Pascal Etienne / Pascal Dumy / Pierre Martineau / Martine Pugnière / Catherine Perrin / Gilles Subra / Ahmad Mehdi

    Molecules, Vol 26, Iss 6085, p

    2021  Band 6085

    Abstract: Ordered mesoporous materials and their modification with multiple functional groups are of wide scientific interest for many applications involving interaction with biological systems and biomolecules (e.g., catalysis, separation, sensor design, nano- ... ...

    Abstract Ordered mesoporous materials and their modification with multiple functional groups are of wide scientific interest for many applications involving interaction with biological systems and biomolecules (e.g., catalysis, separation, sensor design, nano-science or drug delivery). In particular, the immobilization of enzymes onto solid supports is highly attractive for industry and synthetic chemistry, as it allows the development of stable and cheap biocatalysts. In this context, we developed novel silylated amino acid derivatives (Si-AA-NH 2 ) that have been immobilized onto SBA-15 materials in biocompatible conditions avoiding the use of toxic catalyst, solvents or reagents. The resulting amino acid-functionalized materials (SBA-15@AA) were characterized by XRD, TGA, EA, Zeta potential, nitrogen sorption and FT-IR. Differences of the physical properties (e.g., charges) were observed while the structural ones remained unchanged. The adsorption of the enzyme lysozyme (Lyz) onto the resulting functionalized SBA-15@AA materials was evaluated at different pHs. The presence of different functional groups compared with bare SBA-15 showed better adsorption results, for example, 79.6 nmol of Lyz adsorbed per m 2 of SBA-15@Tyr compared with the 44.9 nmol/m 2 of the bare SBA-15.
    Schlagwörter sol–gel ; silylated amino acids ; SBA-15 ; protein adsorption ; lysozyme ; Organic chemistry ; QD241-441
    Thema/Rubrik (Code) 540 ; 500
    Sprache Englisch
    Erscheinungsdatum 2021-10-01T00:00:00Z
    Verlag MDPI AG
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  5. Artikel ; Online: Peptide synthesis

    Ophélie Maurin / Pascal Verdié / Gilles Subra / Frédéric Lamaty / Jean Martinez / Thomas-Xavier Métro

    Beilstein Journal of Organic Chemistry, Vol 13, Iss 1, Pp 2087-

    ball-milling, in solution, or on solid support, what is the best strategy?

    2017  Band 2093

    Abstract: While presenting particularly interesting advantages, peptide synthesis by ball-milling was never compared to the two traditional strategies, namely peptide syntheses in solution and on solid support (solid-phase peptide synthesis, SPPS). In this study, ... ...

    Abstract While presenting particularly interesting advantages, peptide synthesis by ball-milling was never compared to the two traditional strategies, namely peptide syntheses in solution and on solid support (solid-phase peptide synthesis, SPPS). In this study, the challenging VVIA tetrapeptide was synthesized by ball-milling, in solution, and on solid support. The three strategies were then compared in terms of yield, purity, reaction time and environmental impact. The results obtained enabled to draw some strengths and weaknesses of each strategy, and to foresee what will have to be implemented to build more efficient and sustainable peptide syntheses in the near future.
    Schlagwörter ball-mill ; green chemistry ; mechanochemistry ; peptide synthesis ; SPPS ; Science ; Q ; Organic chemistry ; QD241-441
    Sprache Englisch
    Erscheinungsdatum 2017-10-01T00:00:00Z
    Verlag Beilstein-Institut
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  6. Artikel ; Online: Hydrocarbon-Stapled Peptide Based-Nanoparticles for siRNA Delivery

    Matthieu Simon / Nabila Laroui / Marianne Heyraud / Guillaume Laconde / Lamiaa M. A. Ali / Kevin Bourbiaux / Gilles Subra / Lubomir L. Vezenkov / Baptiste Legrand / Muriel Amblard / Nadir Bettache

    Nanomaterials, Vol 10, Iss 2334, p

    2020  Band 2334

    Abstract: Small interfering RNAs (siRNAs) are promising molecules for developing new therapies based on gene silencing; however, their delivery into cells remains an issue. In this study, we took advantage of stapled peptide technology that has emerged as a ... ...

    Abstract Small interfering RNAs (siRNAs) are promising molecules for developing new therapies based on gene silencing; however, their delivery into cells remains an issue. In this study, we took advantage of stapled peptide technology that has emerged as a valuable strategy to render natural peptides more structured, resistant to protease degradation and more bioavailable, to develop short carriers for siRNA delivery. From the pool of stapled peptides that we have designed and synthesized, we identified non-toxic vectors that were able to efficiently encapsulate siRNA, transport them into the cell and induce gene silencing. Remarkably, the most efficient stapled peptide (JMV6582), is composed of only eight amino-acids and contains only two cationic charges.
    Schlagwörter CPP ; Stapled peptides ; siRNA ; gene silencing ; Chemistry ; QD1-999
    Sprache Englisch
    Erscheinungsdatum 2020-11-01T00:00:00Z
    Verlag MDPI AG
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  7. Artikel ; Online: Design of PEGylated Three Ligands Silica Nanoparticles for Multi-Receptor Targeting

    Manon Maurel / Titouan Montheil / Julie Martin / Line Chaar / Veronica Guzman-Gonzalez / Morgane Couvet / Thibault Jacquet / Tao Jia / Beatrice Eymin / Karine Parra / Pascal Dumy / Jean Martinez / Florence Ruggiero / Elisabeth Vaganay / Ahmad Mehdi / Jean-Luc Coll / Gilles Subra

    Nanomaterials, Vol 11, Iss 1, p

    2021  Band 177

    Abstract: The synthesis of silica nanoparticles (SiNPs) decorated on their surface with a range of various elements (e.g., ligands, drugs, fluorophores, vectors, etc.) in a controlled ratio remains a big challenge. We have previously developed an efficient ... ...

    Abstract The synthesis of silica nanoparticles (SiNPs) decorated on their surface with a range of various elements (e.g., ligands, drugs, fluorophores, vectors, etc.) in a controlled ratio remains a big challenge. We have previously developed an efficient strategy to obtain in one-step, well-defined multifunctional fluorescent SiNPs displaying fluorophores and two peptides ligands as targeting elements, allowing selective detection of cancer cells. In this paper, we demonstrate that additional level of controlled multifunctionality can be achieved, getting even closer to the original concept of “magic bullet”, using solely sol–gel chemistry to achieve conjugation of PEG chains for stealth, along with three different ligands. In addition, we have answered the recurrent question of the surface ungrafting by investigating the stability of different siloxane linkages with the ERETIC Method (Electronic Reference to Access In Vivo Concentrations) by 19 F NMR quantification. We also compared the efficiency of the hybrid silylated fluorophore covalent linkage in the core of the SiNP to conventional methods. Finally, the tumor-cell-targeting efficiency of these multi-ligand NPs on human endothelial cells (HUVEC or HDMEC) and mixed spheroids of human melanoma cells and HUVEC displaying different types of receptors were evaluated in vitro.
    Schlagwörter silica nanoparticles ; silylated peptides ; sol–gel ; fluorophore ; surface functionalization ; cancer targeting ; Chemistry ; QD1-999
    Thema/Rubrik (Code) 620
    Sprache Englisch
    Erscheinungsdatum 2021-01-01T00:00:00Z
    Verlag MDPI AG
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  8. Artikel: Site-specific grafting on titanium surfaces with hybrid temporin antibacterial peptides

    Masurier, Nicolas / Jean-Baptiste Tissot / Douae Boukhriss / Said Jebors / Coline Pinese / Pascal Verdié / Muriel Amblard / Ahmad Mehdi / Jean Martinez / Vincent Humblot / Gilles Subra

    Journal of materials chemistry. 2018 Mar. 21, v. 6, no. 12

    2018  

    Abstract: Relying on a membrane-disturbing mechanism of action and not on any intracellular target, antimicrobial peptides (AMP) are attractive compounds to be grafted on the surface of implantable materials such as silicone catheters or titanium surgical implants. ...

    Abstract Relying on a membrane-disturbing mechanism of action and not on any intracellular target, antimicrobial peptides (AMP) are attractive compounds to be grafted on the surface of implantable materials such as silicone catheters or titanium surgical implants. AMP sequences often display numerous reactive functions (e.g. amine, carboxylic acid) on their side chains and straightforward conjugation chemistries could lead to uncontrolled covalent grafting, random orientation, and non-homogenous density. To achieve an easy and site specific covalent attachment of unprotected peptides on titanium surfaces, we designed hybrid silylated biomolecules based on the temporin-SHa amphipathic helical antimicrobial sequence. With the grafting reaction being chemoselective, we designed five analogues displaying the silane anchoring function at the N-ter, C-ter or at different positions inside the sequence to get an accurate control of the orientation. Grafting density calculations were performed by XPS and the influence of the orientation of the peptide on the surface was clearly demonstrated by the measure of antimicrobial activity. Temporin amphipathic helices are described to permeabilize the bacterial membrane by interacting in a parallel orientation with it. Our results move in the direction of this mechanism as the selective grafting of hybrid temporin 2 through a lysine placed at the center of the peptide sequence, resulted in better biofilm growth inhibition of E. coli and S. epidermis than substrates in which temporins were grafted via their C- or N-terminus.
    Schlagwörter Escherichia coli ; X-ray photoelectron spectroscopy ; antimicrobial peptides ; antimicrobial properties ; biofilm ; carboxylic acids ; catheters ; chemoselectivity ; growth retardation ; lysine ; mechanism of action ; silane ; silicone ; surfactants ; titanium
    Sprache Englisch
    Erscheinungsverlauf 2018-0321
    Umfang p. 1782-1790.
    Erscheinungsort The Royal Society of Chemistry
    Dokumenttyp Artikel
    ZDB-ID 2702241-9
    ISSN 2050-7518 ; 2050-750X
    ISSN (online) 2050-7518
    ISSN 2050-750X
    DOI 10.1039/c8tb00051d
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  9. Artikel ; Online: Investigation of Elemental Mass Spectrometry in Pharmacology for Peptide Quantitation at Femtomolar Levels.

    Emmanuelle Cordeau / Carine Arnaudguilhem / Brice Bouyssiere / Agnès Hagège / Jean Martinez / Gilles Subra / Sonia Cantel / Christine Enjalbal

    PLoS ONE, Vol 11, Iss 6, p e

    2016  Band 0157943

    Abstract: In the search of new robust and environmental-friendly analytical methods able to answer quantitative issues in pharmacology, we explore liquid chromatography (LC) associated with elemental mass spectrometry (ICP-MS) to monitor peptides in such complex ... ...

    Abstract In the search of new robust and environmental-friendly analytical methods able to answer quantitative issues in pharmacology, we explore liquid chromatography (LC) associated with elemental mass spectrometry (ICP-MS) to monitor peptides in such complex biological matrices. The novelty is to use mass spectrometry to replace radiolabelling and radioactivity measurements, which represent up-to now the gold standard to measure organic compound concentrations in life science. As a proof of concept, we choose the vasopressin (AVP)/V1A receptor system for model pharmacological assays. The capacity of ICP-MS to provide highly sensitive quantitation of metallic and hetero elements, whatever the sample medium, prompted us to investigate this technique in combination with appropriate labelling of the peptide of interest. Selenium, that is scarcely present in biological media, was selected as a good compromise between ICP-MS response, covalent tagging ability using conventional sulfur chemistry and peptide detection specificity. Applying selenium monitoring by elemental mass spectrometry in pharmacology is challenging due to the very high salt content and organic material complexity of the samples that produces polyatomic aggregates and thus potentially mass interferences with selenium detection. Hyphenation with a chromatographic separation was found compulsory. Noteworthy, we aimed to develop a straightforward quantitative protocol that can be performed in any laboratory equipped with a standard macrobore LC-ICP-MS system, in order to avoid time-consuming sample treatment or special implementation of instrumental set-up, while allowing efficient suppression of all mass interferences to reach the targeted sensitivity. Significantly, a quantification limit of 57 ng Se L-1 (72 femtomoles of injected Se) was achieved, the samples issued from the pharmacological assays being directly introduced into the LC-ICP-MS system. The established method was successfully validated and applied to the measurement of the vasopressin ligand ...
    Schlagwörter Medicine ; R ; Science ; Q
    Thema/Rubrik (Code) 540
    Sprache Englisch
    Erscheinungsdatum 2016-01-01T00:00:00Z
    Verlag Public Library of Science (PLoS)
    Dokumenttyp Artikel ; Online
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  10. Artikel: Heteromultivalent targeting of integrin αvβ3 and neuropilin 1 promotes cell survival via the activation of the IGF1/insulin receptors

    Jia, Tao / Ahmad Mehdi / Béatrice Eymin / Gilles Subra / Jean Martinez / Jean-Luc Coll / Jéremy Ciccione / Jungyoon Choi / Maxime Henry

    Biomaterials. 2017,

    2017  

    Abstract: Angiogenesis strongly depends on the activation of integrins, especially integrin αvβ3, and of neuropilin-1 (NRP-1), a co-receptor of VEGFR2. Dual-targeted molecules that simultaneously block both of them are expected have increased anti-angiogenic and ... ...

    Abstract Angiogenesis strongly depends on the activation of integrins, especially integrin αvβ3, and of neuropilin-1 (NRP-1), a co-receptor of VEGFR2. Dual-targeted molecules that simultaneously block both of them are expected have increased anti-angiogenic and antitumor activity. Toward this goal, we generated bifunctional 40 nm-sized silica nanoparticles (NPs) coated with controlled amounts of cRGD and ATWLPPR peptides and studied their affinity, selectivity and biological activity in HUVECs. Sub-nanomolar concentrations of NPs grafted either with ATWLPPR alone or in combination with cRGD exhibit potent and specific antagonist activity against VEGFR2/AKT signaling. However, a 1 nM concentration of the cRGD/ATWLPPR-heteromultivalent particles (RGD/ATW-NPs) also blocks the phosphorylation of VEGFR2 while co-inducing an unexpected long-lasting activation of AKT via IGF-1R/IR-AKT/GSK3β/eNOS signaling that stimulates cell survival and abrogates the intrinsic toxicity of silica-NPs to serum-starved HUVECs. We also showed that their repeated intravenous administration was associated with the proliferation of human U87MG tumor cells engrafted in nude mice and a dilatation of the tumor blood vessels.We present biochemical evidence for the complex cross-talk generated by the binding of the heteromultivalent NPs with αvβ3-integrin and with NRP1. In particular, we show for the first time that such heteromultivalent NPs can trans-activate IGF1R and exert dose-dependent pro-survival activity. This study demonstrates the difficulties in designing targeted silica-based NPs for antiangiogenic therapies and the possible risks posed by undesirable side effects.
    Schlagwörter adverse effects ; angiogenesis ; antagonists ; antineoplastic activity ; blood ; cell viability ; dose response ; humans ; integrins ; intravenous injection ; mice ; nanoparticles ; neoplasm cells ; peptides ; phosphorylation ; receptors ; risk ; silica ; toxicity ; vascular endothelial growth factor receptor-2
    Sprache Englisch
    Umfang p. .
    Erscheinungsort Elsevier Ltd
    Dokumenttyp Artikel
    Anmerkung Pre-press version
    ZDB-ID 603079-8
    ISSN 0142-9612
    ISSN 0142-9612
    DOI 10.1016/j.biomaterials.2017.10.042
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