Peer-reviewed Publications |
Perez-Lloret M, Fraix A, Petralia S, Conoci, S., Tafani V, Cutrone, G., Vargas-Berenguel, A., Gref R, & Sortino S. (2019). One-Step Photochemical Green Synthesis of Water-Dispersible Ag, Au, and Au@Ag Core-Shell Nanoparticles. Chemistry, 25(64), 14638.
Résumé: A simple and green synthetic protocol for the rapid and effective preparation of Ag, Au and Au@Ag core-shell nanoparticles (NPs) is reported based on the light irradiation of a biocompatible, water-soluble dextran functionalized with benzophenone (BP) in the presence of AgNO3 , HAuCl4 , or both. Photoactivation of the BP moiety produces the highly reducing ketyl radicals through fast (<50 ns) intramolecular H-abstraction from the dextran scaffold, which, in turn, ensures excellent dispersibility of the obtained metal NPs in water. The antibacterial activity of the AgNPs and the photothermal action of the Au@Ag core-shell are also shown.
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Cabriel C,., Bourg N, Jouchet, P., Dupuis, G., Leterrier, C., Baron A, Badet-Denisot, M. - A., Vauzeilles,, Fort, E.,, & Leveque-Fort S. (2019). Combining 3D single molecule localization strategies for reproducible bioimaging. Nat Commun, 10, 1980.
Résumé: Here, we present a 3D localization-based super-resolution technique providing a slowly varying localization precision over a 1 mum range with precisions down to 15 nm. The axial localization is performed through a combination of point spread function (PSF) shaping and supercritical angle fluorescence (SAF), which yields absolute axial information. Using a dual-view scheme, the axial detection is decoupled from the lateral detection and optimized independently to provide a weakly anisotropic 3D resolution over the imaging range. This method can be readily implemented on most homemade PSF shaping setups and provides drift-free, tilt-insensitive and achromatic results. Its insensitivity to these unavoidable experimental biases is especially adapted for multicolor 3D super-resolution microscopy, as we demonstrate by imaging cell cytoskeleton, living bacteria membranes and axon periodic submembrane scaffolds. We further illustrate the interest of the technique for biological multicolor imaging over a several-mum range by direct merging of multiple acquisitions at different depths.
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Cutrone G, Q. J., Menendez-Miranda M, Casas-Solvas JM, Aykaç A, Li X, Foulkes D, Moreira-Alvarez B, Encinar JR, Ladavière C, Desmaële D, Vargas-Berenguel A, Gref R. (2019). Comb-like dextran copolymers: A versatile strategy to coat highly porous MOF nanoparticles with a PEG shell. Carbohydr Polym, 223, 115085.
Résumé: Nanoparticles made of metal-organic frameworks (nanoMOFs) are becoming of increasing interest as drug carriers. However, engineered coatings such as poly(ethylene glycol) (PEG) based ones are required to prevent nanoMOFs recognition and clearance by the innate immune system, a prerequisite for biomedical applications. This still presents an important challenge due to the highly porous structure and degradability of nanoMOFs. We provide here a proof of concept that the surface of iron-based nanoMOFs can be functionalized in a rapid, organic solvent-free and non-covalent manner using a novel family of comb-like copolymers made of dextran (DEX) grafted with both PEG and alendronate (ALN) moieties, which are iron complexing groups to anchor to the nanoMOFs surface. We describe the synthesis of DEX-ALN-PEG copolymers by click chemistry, with control of both the amount of PEG and ALN moieties. Stable DEX-ALN-PEG coatings substantially decreased their internalization by macrophages in vitro, providing new perspectives for biomedical applications.
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Jian Xu, L. W., Tao Guo, Guoqing Zhang, Caifen Wang, Haiyan Li, Xue Li, Vikramjeet Singh, Weidong Chen, Ruxandra Gref, Jiwen Zhang. (2019). A “Ship-in-a-Bottle” strategy to create folic acid nanoclusters inside the nanocages of gamma-cyclodextrin metal-organic frameworks. Int J Pharm, 556, 89.
Résumé: Assembled between gamma-cyclodextrins (CD) and potassium ions, gamma-cyclodextrin metal-organic frameworks (CD-MOF) create spatially extended and ordered cage-like structures. Herein, it was demonstrated that folic acid (FA), a model molecule, could be densely packed inside CD-MOF reaching 2:1 FA:CD molar ratio. This “Ship-in-a-Bottle” strategy leads to a 1450 fold increase of the apparent solubility of FA. Moreover, the bioavailability of FA inside CD-MOF in rats was enhanced by a factor of 1.48 as compared to free FA. The unique mechanism of FA incorporation in the CD-MOF 3D network was also explored, which was different from the conventional CD inclusion complexation. Taylor dispersion investigations indicated that FA was incorporated on the basis of a two-component model, which was further supported by a set of complementary methods, including SEM, XRPD, BET, SR-FTIR, SAXS and molecular simulation. The hypothesized mechanism suggested that: i) tiny FA nanoclusters formed inside the hydrophilic cavities and onto the surface of CD-MOF and ii) FA was included inside dual-CD units in CD-MOF. In a nutshell, this dual incorporation mechanism is an original approach to dramatically increase the drug apparent solubility and bioavailability, and could be a promising strategy for other poorly soluble drugs.
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Li, X., Semiramoth, N., Hall, S., Tafani, V., Josse, J., Laurent, F., Salzano, G., Foulkes, D., Brodin, P., Majlessi, L., Ghermani, N. ‐E., Maurin, G., Couvreur, P., Serre, C., Bernet‐Camard, M. ‐F., Zhang, J., & Gref, R. (2019). Combinatorial Drug Therapy: Compartmentalized Encapsulation of Two Antibiotics in Porous Nanoparticles: an Efficient Strategy to Treat Intracellular Infections (Part. Part. Syst. Charact. 3/2019). Part. Part. Syst. Charact., 36(3), 1970009.
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Li, X., Semiramoth, N., Hall, S., Tafani, V., Josse, J., Laurent, F., Salzano, G., Foulkes, D., Brodin, P., Majlessi, L., Ghermani, N. ‐E., Maurin, G., Couvreur, P., Serre, C., Bernet‐Camard, M. ‐F., Zhang, J., & Gref, R. (2019). Compartmentalized Encapsulation of Two Antibiotics in Porous Nanoparticles: an Efficient Strategy to Treat Intracellular Infections. Part. Part. Syst. Charact., 36(3), 1800360.
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Porcino, M., Christodoulou, I., Vuong, M. D. L., Gref, R., & Martineau-Corcos, C. (2019). New insights on the supramolecular structure of highly porous core–shell drug nanocarriers using solid-state NMR spectroscopy. RSC Adv., 9(56), 89.
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Yuanzhi He, W. Z., Tao Guo, Guoqing Zhang, Wei Qin, Liu Zhang, Caifen Wang, Weifeng Zhu, Ming Yang, Xiaoxiao Hu, Vikramjeet Singh, Li Wu, Ruxandra Gref, Jiwen Zhang. (2019). Drug nanoclusters formed in confined nano-cages of CD-MOF: dramatic enhancement of solubility and bioavailability of azilsartan. Acta Pharm Sin B, 9(1), 97.
Résumé: Tremendous efforts have been devoted to the enhancement of drug solubility using nanotechnologies, but few of them are capable to produce drug particles with sizes less than a few nanometers. This challenge has been addressed here by using biocompatible versatile gamma-cyclodextrin (gamma-CD) metal-organic framework (CD-MOF) large molecular cages in which azilsartan (AZL) was successfully confined producing clusters in the nanometer range. This strategy allowed to improve the bioavailability of AZL in Sprague-Dawley rats by 9.7-fold after loading into CD-MOF. The apparent solubility of AZL/CD-MOF was enhanced by 340-fold when compared to the pure drug. Based on molecular modeling, a dual molecular mechanism of nanoclusterization and complexation of AZL inside the CD-MOF cages was proposed, which was confirmed by small angle X-ray scattering (SAXS) and synchrotron radiation-Fourier transform infrared spectroscopy (SR-FTIR) techniques. In a typical cage-like unit of CD-MOF, three molecules of AZL were included by the gamma-CD pairs, whilst other three AZL molecules formed a nanocluster inside the 1.7nm sized cavity surrounded by six gamma-CDs. This research demonstrates a dual molecular mechanism of complexation and nanoclusterization in CD-MOF leading to significant improvement in the bioavailability of insoluble drugs.
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Jain-Beuguel C, Li, X., Houel-Renault, L., Modjinou T, Gref R, Renard, E., & Langlois V. (2019). Water-Soluble Poly(3-hydroxyalkanoate) Sulfonate: Versatile Biomaterials Used as Coatings for Highly Porous Nano-Metal Organic Framework. (Vol. 20).
Résumé: Water-soluble poly(3-hydroxyalkanoate) containing ionic groups were designed by two successive photoactivated thiol-ene reactions. Sodium-3-mercapto-1-ethanesulfonate (SO3(-)) and poly(ethylene glycol) (PEG) methyl ether thiol were grafted onto poly(3-hydroxyoctanoate-co-3-hydroxyundecenoate) PHO(67)U(33) to introduce both ionic groups and hydrophilic moieties. The grafted copolymers PHO(67)SO3(-)(20)PEG(13) were then used as biocompatible coatings of nano-metal organic frameworks (nanoMOFs) surfaces. Scanning electron microscopy and scanning transmission electron microscopy coupled with energy dispersive X-ray characterizations have clearly demonstrated the presence of the copolymer on the MOF surface. These coated nanoMOFs are stable in aqueous and physiological fluids. Cell proliferation and cytotoxicity tests performed on murine macrophages J774.A1 revealed no cytotoxic side effect. Thus, biocompatibility and stability of these novel hybrid porous MOF structures encourage their use in the development of effective therapeutic nanoparticles.
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Jain-Beuguel, C., Li, X., Houel-Renault, L., Modjinou, T., Simon-Colin, C., Gref, R., Renard E, & Langlois V. (2019). Water-Soluble Poly(3-hydroxyalkanoate) Sulfonate: Versatile Biomaterials Used as Coatings for Highly Porous Nano-Metal Organic Framework. (Vol. 20).
Résumé: Water-soluble poly(3-hydroxyalkanoate) containing ionic groups were designed by two successive photoactivated thiol-ene reactions. Sodium-3-mercapto-1-ethanesulfonate (SO3(-)) and poly(ethylene glycol) (PEG) methyl ether thiol were grafted onto poly(3-hydroxyoctanoate-co-3-hydroxyundecenoate) PHO(67)U(33) to introduce both ionic groups and hydrophilic moieties. The grafted copolymers PHO(67)SO3(-)(20)PEG(13) were then used as biocompatible coatings of nano-metal organic frameworks (nanoMOFs) surfaces. Scanning electron microscopy and scanning transmission electron microscopy coupled with energy dispersive X-ray characterizations have clearly demonstrated the presence of the copolymer on the MOF surface. These coated nanoMOFs are stable in aqueous and physiological fluids. Cell proliferation and cytotoxicity tests performed on murine macrophages J774.A1 revealed no cytotoxic side effect. Thus, biocompatibility and stability of these novel hybrid porous MOF structures encourage their use in the development of effective therapeutic nanoparticles.
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Pastor A,, Machelart A,, Li X,, Willand N,., Baulard A, Brodin, P., Gref R, & Desmaele D. (2019). A novel codrug made of the combination of ethionamide and its potentiating booster: synthesis, self-assembly into nanoparticles and antimycobacterial evaluation. (Vol. 17).
Résumé: Ethionamide (ETH) is one of the most widely used second-line chemotherapeutic drugs for the treatment of multi-drug-resistant tuberculosis. The bioactivation and activity of ETH is dramatically potentiated by a family of molecules called “boosters” among which BDM43266 is one of the most potent. However, the co-administration of these active molecules is hampered by their low solubility in biological media and by the strong tendency of ETH to crystallize. A novel strategy that involves synthesizing a codrug able to self-associate into nanoparticles prone to be taken up by infected macrophages is proposed here. This codrug is designed by tethering N-hydroxymethyl derivatives of both ETH and its booster through a glutaric linker. This codrug self-assembles into nanoparticles of around 200 nm, stable upon extreme dilution without disaggregating as well as upon concentration. The nanoparticles of the codrug can be intranasally administered overcoming the unfavorable physico-chemical profiles of the parent drugs. Intrapulmonary delivery of the codrug nanoparticles to Mtb infected mice via the intranasal route at days 7, 9, 11, 14, 16 and 18 post-infection reduces the bacterial load in the lungs by a factor of 6.
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Shailendra Shakya, Y. H., Xiaohong Ren, Tao Guo, Abi Maharjan, Ting Luo, Tingting Wang, Ramesh Dhakhwa, Balmukunda Regmi, Haiyan Li, Ruxandra Gref, Jiwen Zhang. (2019). Ultrafine Silver Nanoparticles Embedded in Cyclodextrin Metal-Organic Frameworks with GRGDS Functionalization to Promote Antibacterial and Wound Healing Application. (Vol. 15).
Résumé: The challenge of bacterial infection increases the risk of mortality and morbidity in acute and chronic wound healing. Silver nanoparticles (Ag NPs) are a promising new version of conventional antibacterial nanosystem to fight against the bacterial resistance in concern of the drug discovery void. However, there are several challenges in controlling the size and colloidal stability of Ag NPs, which readily aggregate or coalesce in both solid and aqueous state. In this study, a template-guided synthesis of ultrafine Ag NPs of around 2 nm using water-soluble and biocompatible gamma-cyclodextrin metal-organic frameworks (CD-MOFs) is reported. The CD-MOF based synthetic strategy integrates AgNO3 reduction and Ag NPs immobilization in one pot achieving dual functions of reduced particle size and enhanced stability. Meanwhile, the synthesized Ag NPs are easily dispersible in aqueous media and exhibit effective bacterial inhibition. The surface modification of cross-linked CD-MOF particles with GRGDS peptide boosts the hemostatic effect that further enhances wound healing in synergy with the antibacterial effect. Hence, the strategy of ultrafine Ag NPs synthesis and immobilization in CD-MOFs together with GRGDS modification holds promising potential for the rational design of effective wound healing devices.
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