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Simple Summary γ-H2AX, a phosphorylated variant of histone H2A, is a widely used biomarker of DNA replication stress. To develop an immunological probe able to detect and track γ-H2AX in live cancer cells, we have isolated single domain antibodies (called nanobodies) that are easily expressed as functional recombinant proteins and here we report the extensive characterization of a novel nanobody that specifically recognizes γ-H2AX. The interaction of this nanobody with the C-terminal end of γ-H2AX was determined by X-ray crystallography. Moreover, the generation of a bivalent nanobody allowed us to precisely detect γ-H2AX foci in drug-treated cells as efficiently as with commercially available conventional antibodies. Furthermore, we tracked γ-H2AX foci in live cells upon intracellular delivery of the bivalent nanobody fused to the red fluorescent protein dTomato, making, consequently, this new cost-effective reagent useful for studying drug-induced replication stress in both fixed and living cancer cells. Abstract Histone H2AX phosphorylated at serine 139 (γ-H2AX) is a hallmark of DNA damage, signaling the presence of DNA double-strand breaks and global replication stress in mammalian cells. While γ-H2AX can be visualized with antibodies in fixed cells, its detection in living cells was so far not possible. Here, we used immune libraries and phage display to isolate nanobodies that specifically bind to γ-H2AX. We solved the crystal structure of the most soluble nanobody in complex with the phosphopeptide corresponding to the C-terminus of γ-H2AX and show the atomic constituents behind its specificity. We engineered a bivalent version of this nanobody and show that bivalency is essential to quantitatively visualize γ-H2AX in fixed drug-treated cells. After labelling with a chemical fluorophore, we were able to detect γ-H2AX in a single-step assay with the same sensitivity as with validated antibodies. Moreover, we produced fluorescent nanobody-dTomato fusion proteins and applied a transduction strategy to visualize with precision γ-H2AX foci present in intact living cells following drug treatment. Together, this novel tool allows performing fast screenings of genotoxic drugs and enables to study the dynamics of this particular chromatin modification in individual cancer cells under a variety of conditions.

Efficiency of polyethylenimine (PEI) for nucleic acid delivery is affected by the size of the carrier and length of the nucleic acids. For instance, PEIs with molecular weights between 10-30kDa provide optimal DNA delivery activity whereas PEIs with molecular weights below 1.8kDa are ineffective. The activity of PEI is also severely diminished by substitution of DNA for shorter nucleic acids such as mRNA or siRNA. Here, through chemical modification of the primary amines to aromatic domains we achieved nucleic acid delivery by the 1.8kDa polyethylenimine (PEI) particles. This modification did not affect the PEI buffering abilities but enhanced its pH-sensitive aggregation, enabling stabilization of the polyplex outside the cell while still allowing nucleic acid release following cellular entry. The aromatic PEIs were then evaluated for their gene, mRNA, siRNA and 2'O-methyl phosphorothioate oligonucleotide in vitro transfection abilities. The salicylamide-grafted PEI showed to be a reliable carrier for delivering nucleic acids with cytoplasmic activity such as the mRNA and siRNA or nuclear diffusible oligonucleotide. It was then further equipped with polyethyleneglycol (PEG) and the delivery efficiency of the copolymer was tested in vivo for regeneration of dystrophin in the muscle of mdx mouse through a 2'O-methyl phosphorothioate-mediated splicing modulation. Intramuscular administration of polyplexes resulted in dystrophin-positive fibers in a mouse model of Duchenne muscular dystrophy without apparent toxicity. These findings indicate that precise modifications of low molecular weight PEI improve its bio-responsiveness and yield delivery vehicles for nucleic acids of various types in vitro and in vivo.

Noninvasive diagnostic by imaging combined with a contrast agent (CA) is by now the most used technique to get insight into human bodies. X-ray and magnetic resonance imaging (MRI) are widely used technologies providing complementary results. Nowadays, it seems clear that bimodal CAs could be an emerging approach to increase the patient compliance, accessing different imaging modalities with a single CA injection. Owing to versatile designs, targeting properties, and high payload capacity, nanocarriers are considered as a viable solution to reach this goal. In this study, we investigated efficient superparamagnetic iron oxide nanoparticle (SPION)-loaded iodinated nano-emulsions (NEs) as dual modal injectable CAs for X-ray imaging and MRI. The strength of this new CA lies not only in its dual modal contrasting properties and biocompatibility, but also in the simplicity of the nanoparticulate assembling: iodinated oily core was synthesized by the triiodo-benzene group grafting on vitamin E (41.7% of iodine) via esterification, and SPIONs were produced by thermal decomposition during 2, 4, and 6 h to generate SPIONs with different morphologies and magnetic properties. SPIONs with most anisotropic shape and characterized by the highest r2/ r1 ratio once encapsulated into iodinated NE were used for animal experimentation. The in vivo investigation showed an excellent contrast modification because of the presence of the selected NEs, for both imaging techniques explored, that is, MRI and X-ray imaging. This work provides the description and in vivo application of a simple and efficient nanoparticulate system capable of enhancing contrast for both preclinical imaging modalities, MRI, and computed tomography.

For biological and medical applications, a definable nanomaterial and knowledge on its fate after administration are highly recommended if not mandatory. Here, we synthesized a water-soluble gold nanocluster by sodium borohydride reduction of chloroauric acid in the presence of 5,5′-dithio-bis(2-nitrobenzoic acid). The resulting gold nanocluster displayed the physical characteristics of a cluster containing an inner core of about 100 gold atoms that was surrounded by an organic monolayer made of about 30 thioaminobenzoic acids (TAB) and 14 anionic thionitrobenzoic acids (TNB). The mixed TAB-,TNB-protected gold nanocluster reacted well in water with thiolated peptides containing a nuclear localization signal (NLS) or a nuclear export signal (NES) mainly by exchange of the TNB, providing gold nanoclusters equipped with 8–9 intracellular active peptides and a remaining ligand coverage consisting mostly of the zwitterion TAB. The behavior of these peptide–gold nanoclusters inside the cytosol and nucleus of cells was then assayed using an electroporation procedure allowing transient plasma membrane permeability. Light and electron microscopy observations demonstrated a consistent inflow and diffusion of the gold nanoclusters into the cytosol. Inside the living cells, the distribution of the gold nanoparticles was specifically driven by the appended signal peptides in a manner similar to the distribution of NLS and NES-bearing proteins, demonstrating diffusion ability, stability, and usage of these definable ligand-substituted gold nanoclusters for intracellular applications.

This study aimed to investigate the impact of the size of X-ray iodinated contrast agent in nano-emulsions, on their toxicity and fate in vivo.A new compound, triiodobenzoate cholecalciferol, was synthetized, formulated as nano-emulsions, and followed after i.v. administration in mice by X-ray imaging (micro computed tomography). Physicochemical characterization and process optimization allowed identifying a good compromise between X-ray contrasting properties, monodispersity and stability. This also allowed selecting two formulations with different sizes, hydrodynamic diameters of 55 and 100 nm, but exactly the same composition. In vitro experiments were performed on two cell lines, namely hepatocytes (BNL-CL2) and macrophages (RAW264.7).Cell viability studies, cell uptake observations by confocal microscopy, and uptake quantification by fluorimetry, disclosed clear differences between two formulations, as well as between two types of cell lines. After i.v. injection of the two iodinated nano-emulsions in mice, CT scans provided the quantification of the pharmacokinetics and biodistributions. We finally showed that the size in the nano-emulsions has not a real impact on the pharmacokinetics and biodistributions, but has a strong influence on their toxicity, corroborating the in vitro results.This study shows that the size of the nanocarrier significantly matters, likely due to highly different interactions with cells and tissues. Graphical Abstract A study on the effect of the size of cholecciferol nano-emulsions, on their in vivo becoming, through X-ray imaging modality.

Phosphorylated histone H2AX (&gamma, H2AX), a central player in the DNA damage response (DDR), serves as a biomarker of DNA double-strand break repair. Although DNA damage is generally visualized by the formation of &gamma, H2AX foci in injured nuclei, it is unclear whether the widespread uniform nuclear &gamma, H2AX (called pan-nuclear) pattern occurring upon intense replication stress (RS) is linked to DDR. Using a novel monoclonal antibody that binds exclusively to the phosphorylated C-terminus of H2AX, we demonstrate that H2AX phosphorylation is systematically pan-nuclear in cancer cells stressed with RS-inducing drugs just before they die. The pan-nuclear &gamma, H2AX pattern is abolished by inhibition of the DNA-PK kinase. Cell death induction of cancer cells treated with increasing combinations of replication and kinase (ATR and Chk1) inhibitory drugs was proportional to the appearance of pan-nuclear &gamma, H2AX pattern. Delivery of labeled anti-&gamma, H2AX Fabs in stressed cells demonstrated at a single cell level that pan-nuclear &gamma, H2AX formation precedes irreversible cell death. Moreover, we show that H2AX is not required for RS-induced cell death in HeLa cells. Thus, the nuclear-wide formation of &gamma, H2AX is an incident of RS-induced cell death and, thus, the pan nuclear H2AX pattern should be regarded as an indicator of lethal RS-inducing drug efficacy.

International audience; We report the efficient one-step synthesis and detailed physicochemical evaluation of novel biocompatible nanosystems useful for cancer therapeutics and diagnostics (theranostics). These systems are the superparamagnetic iron oxide nanoparticles (SPIONs) carrying the anticancer drug doxorubicin and coated with the covalently bonded biocompatible polymer poly(ethylene glycol) (PEG), native and modified with the biological cancer targeting ligand folic acid (PEG-FA). These multifunctional nanoparticles (SPION-DOX-PEG-FA) are designed to rationally combine multilevel mechanisms of cancer cell targeting (magnetic and biological), bimodal cancer cell imaging (by means of MRI and fluorescence), and bimodal cancer treatment (by targeted drug delivery and by hyperthermia effect). Nevertheless, for these concepts to work together, the choice of ingredients and particle structure are critically important. Therefore, in the present work, a detailed physicochemical characterization of the organic coating of the hybrid nanoparticles is performed by several surface-specific instrumental methods, including surface-enhanced Raman scattering (SERS) spectroscopy, X-ray photoelectron spectrometry (XPS), and time-of-flight secondary ion mass spectrometry (ToF-SIMS). We demonstrate that the anticancer drug doxorubicin is attached to the iron oxide surface and buried under the polymer layers, while folic acid is located on the extreme surface of the organic coating. Interestingly, the moderate presence of folic acid on the particle surface does not increase the particle surface potential, while it is sufficient to increase the particle uptake by MCF-7 cancer cells. All of these original results contribute to the better understanding of the structure–activity relationship for hybrid biocompatible nanosystems and are encouraging for the applications in cancer theranostics.

Bis(terpyridine) and metallo-bis(terpyridine) Pluronics have been synthesized starting from commercially available P105 and P123 hydroxytelechelic Pluronics. The grafting of terpyridine ligands at the extremity of the Pluronic chains results in the further association of the Pluronic micelles in water. Increasing temperature decreases the solubility of the Pluronics, but also increases the solubility of the terpyridine groups. The addition of 0.5 equiv. nickel(II) ions compared to terpyridine groups induces the formation of bis(terpyridine) nickel(II) complexes and disrupts the initial hydrophobic terpyridine aggregates. In that case, formation of flower-like micelles in which the coronal chains form loops due to the terpyridine nickel(II) complexes is observed in the dilute regime.

A Williamson type etherification approach was applied for the reaction of 4′-chloro-2,2′:6′,2′′-terpyridine with a number of well-defined mono - and bis -hydroxy functionalized polymers, namely poly(tetrahydrofuran), poly(2-ethyl-2-oxazoline) and Pluronics®. The resulting terpyridine functionalized polymers were characterized by 1 H NMR spectroscopy and SEC, as well as MALDI-TOF-MS demonstrating the successful functionalization. This type of end-functionalized chelating macromolecules could be considered as key candidates for the preparation of metallo-supramolecular polymers via metallo-terpyridine complexation; the principle feasibility was demonstrated by UV–vis titration of iron(II) chloride to bis -terpyridine functionalized poly(tetrahydrofuran).

Metallo-supramolecular chemistry offers possibilities for the construction of stimuli-responsive polymeric materials where the environment can have a large impact on the reversibility and strength of interactions between the individual components. The potential of manipulating the strength of the intermolecular non-covalent bonds can result in impressive modifications of the metallo-supramolecular structure and, subsequently, produces changes in the properties of the designed material. The present feature article provides an overview on recent developments in the field of metallo-polymerization of chelating terpyridyl and analogues ligands. Synthetic strategies are described followed by a discussion regarding the characterization and the application of the reviewed metallo-supramolecular structures, mainly based on terpyridines.

A series of main-chain metallopolymers (P1-P10) was prepared by the self-assembly of rigid-linear p-conjugated bis(terpyridine) monomers (1-10) with Zn11 ions and was fully characterized. The polymerization was additionally confirmed by UV/vis titration experiments, A strong increase in viscosities (around 1.6 times) relative to those of the monomer solutions was found. The thermal stability of P1-P10 compared with that of 1-10 was enhanced as a result of the metallopolymerization. The electro-optical properties of the materials were investigated in detail. Tuning of the electrochemical and photophysical properties was enabled; thus, bright purple to green photoluminescent (PL) emission (PL quantum yields of 0.12-0.81) for P1-P10 was observed in solution with the emission color strongly depending on the nature of the p-conjugated bis(terpyridine) system. Thin homogeneous films of P8 were prepared by solution processing, that is, spin-coating and inkjet-printing, and exhibited intense yellow PL emission in the solid state. © 2009 Wiley Periodicals, Inc.

Four different coil-rod-coil metallo-supramol. amphiphilic copolymers have been synthesized via Ru(II) terpyridine complexation, using monoterpyridine end-functionalized poly(ethylene glycol) as hydrophilic block A and different rigid-rod conjugated ditopic terpyridyl ligands as hydrophobic segment B. Those structures are reminiscent of ABA triblock copolymers. Herein, we report for the first time the synthesis and characterization as well as the photophys. and electrochem. properties of these novel Ru(II) ABA assemblies. The aq. self-assembly of these synthesized materials was studied by cryo-transmission electron microscopy and dynamic light scattering, demonstrating a significant influence of the various middle segments B on the size of the obtained micelles. [on SciFinder (R)]

The authors report on the reversible and selective functionalization of surfaces by using supramol. building blocks. The reversible formation of bis-terpyridine complexes, based on a terpyridine ligand-functionalized monolayer, was used as a versatile supramol. binding motif. Thereby, click chem. was applied to covalently bind an acetylene functionalized Fe(II) bis-terpyridine complex onto azide-terminated self-assembled monolayers. By decomplexation of the formed supramol. complex, the ligand modified monolayer could be obtained. These monolayers were subsequently used for addnl. complexation reactions, resulting in the reversible functionalization of the substrates. The proper choice of the coordinating transition metal ions allows the tuning of the binding strength, as well as the physicochem. properties of the formed complexes and thus an engineering of the surface properties. [on SciFinder (R)]

Terpyridine-modified hydrophobic poly(dimethylsiloxane) and hydrophilic poly(ethylene oxide) were combined to new metallo-supramolecular AB-diblock copolymers by utilizing Ru(II) ions. The polymers were synthesized by hydrosilylation of heteroleptic allyloxy-functionalized Ru(II) complexes. The amphiphilic AB-diblock copolymers were used to prepare micelles in an aqueous environment, which were subsequently characterized by dynamic light scattering and cryogenic transmission electron microscopy.

The synthesis and photophys. properties of an ethynylphenyl-substituted terpyridine ligand L and its corresponding zinc(II) complex [Zn(L)2](PF6)2, serving as model compds. for self-assembling Zn(II)-based metallopolymers suited for photoluminscent and electroluminescent devices, are presented. The UV-vis spectra are characterized, and the photoluminescence quantum yields are detd. The ground-state structures are calcd. by means of DFT, and the structural key features are approved by exptl. as well as by DFT-calcd. Raman spectra. Special attention is paid to the pi-electron delocalization between phenylene (ph) and pyridine (py) and, in particular, to changes in the ph-py bond due to complexation. The DFT-calcd. ph-py bond shortening in [Zn(L)2](PF6)2 compared to L correlates well with the higher wavenumber of the v(ph-py(trig)) vibration, which involves strong ph-py bond stretching. The higher ellipticity in the ph-py bond due to complexation, calcd. according to Bader's QTAIM indicating the pi-character of a bond, is confirmed by the higher Raman intensity of the v(ph-py(trig)) vibration. The electron d. distributions in the ph-py bond between [Zn(L)2](PF6)2 and L are compared in an inter-Delta r plot, which highlights the changes in the bonding situation of the ph-py bond induced by complex forming. [on SciFinder (R)]

Metallo-supramolecular polymers offer attractive possibilities to combine the properties of polymers with the characteristics offered by the metal-ligand coordination. Here we present for the first time the combination of metal-bis(terpyridine) complexes and lower critical solution temperature (LCST) polymers that can be switched by addressing either the thermosensitive polymer or the metal complex. We describe a new strategy for the synthesis of poly(N-isopropylacrylamide) (PNIPAM) end functionalized with a terpyridine moiety, which is further used for the preparation of Fe II and Zn II -bis(terpyridine PNIPAM). The comparison of the LCST behavior of the uncomplexed ligands and their metal complexes that bear different counter ions is included. Furthermore, the switchability of the synthesized Fe II system is demonstrated by a decomplexation reaction followed by the characterization of the uncomplexed ligand.

One of the most important characterization methods for macromolecules is SEC. The main difficulty for this type of measurements concerning metallo-supramolecular polymers based on terpyridines is related to the interaction between the charged supramolecular species and the SEC column material. In this paper, we report new studies on the characterization and the stability of supramolecular polymers based on terpyridine metal complexes utilizing SEC. The main aspects concerning the equilibrium between complexed and uncomplexed species are discussed in detail. The present study reveals a strong relationship between the binding strength of the metal ion used and the stability of the terpyridine metal complex during the SEC measurements, which is in agreement with previously published results regarding the stability of small terpyridine metal complexes in solution. These results can lead to improved analytic possibilities and to a better fundamental understanding of the mentioned metallo-supramolecular polymers. Furthermore, the prepared chain-extended supramolecular-polymer was analyzed by depth-sensing indentation proving an increase in elastic modulus in comparison with the starting material.

Development of novel anticancer formulations is a priority challenge in biomedicine. However, in vitro models based on monolayer cultures (2D) which are currently used for cytotoxicity tests leave much to be desired. More and more attention is focusing on 3D in vitro systems which can better mimic solid tumors. The aim of the study was to develop a novel one-step highly reproducible technique for multicellular tumor spheroid (MTS) formation using synthetic cyclic RGD-peptides, and to demonstrate availability of the spheroids as 3D in vitro model for antitumor drug testing. Cell self-assembly effect induced by addition of both linear and cyclic RGD-peptides directly to monolayer cultures was studied for 12 cell lines of various origins, including tumor cells (e.i. U-87 MG, MCF-7, M-3, HCT-116) and normal cells, in particular L-929, BNL.CL2, HepG2. Cyclo-RGDfK and its modification with triphenylphosphonium cation (TPP), namely cyclo-RGDfK(TPP) in a range of 10-100μM were found to induce spheroid formation. The obtained spheroids were unimodal with mean sizes in a range of 60-120μm depending on cell line and serum content in culture medium. The spheroids were used as 3D in vitro model, in order to evaluate cytotoxicity effects of antitumor drugs (doxorubicin, curcumin, temozolomide). The developed technique could be proposed as a promising tool for in vitro test of novel antitumor drugs.

The human organism and its constituting cells rely on interplay between multiple proteins exerting specific functions. Progress in molecular biotechnologies has facilitated the production of recombinant proteins. When administrated to patients, recombinant proteins can provide important healthcare benefits. To date, most therapeutic proteins must act from the extracellular environment, with their targets being secreted modulators or extracellular receptors. This is because proteins cannot passively diffuse across the plasma membrane into the cytosol. To expand the scope of action of proteins for cytosolic targets (representing more than 40% of the genome) effective methods assisting protein cytosolic entry are being developed. To date, direct protein delivery is extremely tedious and inefficient in cultured cells, even more so in animal models of pathology. Novel techniques are changing this limitation, as recently developed in vitro methods can robustly convey large amount of proteins into cell cultures. Moreover, advances in protein formulation or protein conjugates are slowly, but surely demonstrating efficiency for targeted cytosolic entry of functional protein in vivo in tumor xenograft models. In this review, various methods and recently developed techniques for protein transport into cells are summarized. They are put into perspective to address the challenges encountered during delivery.

In this study, we investigated the role of the chemical nature of the oil droplet core of nano-emulsions used as contrast agents for X-ray imaging on their pharmacokinetics and biodistribution. To this end, we formulated PEGylated nano-emulsions with two iodinated oils (i.e., iodinated monoglyceride and iodinated castor oil) and compared them with another iodinated nano-emulsion based on iodinated vitamin E. By using dynamic light scattering and transmission electron microscopy, the three iodinated nano-emulsions were found to exhibit comparable morphologies, size, and surface composition. Furthermore, they were shown to be endowed with very high iodine concentration, which leads to stronger X-ray attenuation properties as compared to the commercial iodinated nano-emulsion Fenestra VC. The three nano-emulsions were i.v. administered in mice and monitored by microcomputed tomography (micro-CT). They showed high contrast enhancement in blood with similar half-life around 6 h but very different accumulation sites. While iodinated monoglycerides exhibited low accumulation in liver and spleen, high accumulation in spleen was observed for iodinated castor oil and in liver for vitamin E. These data clearly highlighted the important role of the oil composition of the nano-emulsion core to obtain strong X-ray contrast enhancement in specific targets such as liver, spleen, or only blood. These differences in biodistribution were partly attributed to differences in the uptake of the nanodroplets by the macrophages in vitro. Another key feature of these nano-emulsions is their long half-elimination time (several weeks), which offers sufficient retention for micro-CT imaging. This work paves the way for the design of nanoparticulate contrast agents for X-ray imaging of selected organs.

Metallo-supramolecular chemistry offers possibilities for the construction of stimuli-responsive polymeric materials where the environment can have a large impact on the reversibility and strength of interactions between the individual components. The potential of manipulating the strength of the intermolecular non-covalent bonds can result in impressive modifications of the metallo-supramolecular structure and, subsequently, produces changes in the properties of the designed material. The present feature article provides an overview on recent developments in the field of metallo-polymerization of chelating terpyridyl and analogues ligands. Synthetic strategies are described followed by a discussion regarding the characterization and the application of the reviewed metallo-supramolecular structures, mainly based on terpyridines.

A series of nine zinc(II) complexes containing substituted 4'- phenyl-2,2':6',2"-terpyridines as ligands is synthesized and fully characterized. The ground-state structures of four examples are calculated by means of DFT and their structural features are confirmed by experimental Raman spectroscopy. Special focus is placed on the degree of p-electron delocalization between the terpyridine unit and the attached phenyl moiety. Applying Bader's quantum theory of atoms in molecules (QTAIM) and visualizing the electron-density distribution by intermolecular ¿¿ plots reveals an increase in ellipticity-and therefore p-electron delocalization for phenylvinyl-substituted derivatives compared to phenylethynyl-substituted ones. Experimentally, this is verified by spectroscopic means, because an increase in ellipticity goes along with a pronounced decrease of the HOMO-LUMO energy band gap. Overall, the lateral p-conjugated substituents are found to strongly influence the electro-optical properties of the complexes. In solution, the color of emission can be modulated from violet to cyan (425-487 nm) and high quantum yields (FPL up to 0.60) are observed. Thin solid films of the complexes in a matrix of poly(- methyl methacrylate) have been inkjet-printed, and their photophysical behavior (bright emission, FPL up to 0.30) reveals their potential as new emissive materials for applications in light-emitting devices. © 2009 Wiley-VCH Verlag GmbH & Co. KGaA.

Rod-coil tri- and tetra-arm star metallo-supramolecular block copolymers have been synthesized by bis-complex formation between a ¿-terpyridine ruthenium(II) mono-complex poly(ethylene glycol) (PEG) and either a tris-terpyridine or a tetra-terpyridine functionalized conjugated rigid core. This leads to amphiphilic star copolymers in which the tris-terpyridine or the tetra-terpyridine rigid core can be considered as hydrophobic central block and the complexed PEG blocks as hydrophilic segments. The self-assembly of these two metallo-supramolecular star block copolymers has been investigated by dynamic and static light scattering as well as by cryo-transmission electron microscopy in acetone and acetone/water mixtures.

Metallo-supramolecular chemistry offers possibilities for the construction of stimuli-responsive polymeric materials where the environment can have a large impact on the reversibility and strength of interactions between the individual components. The potential of manipulating the strength of the intermolecular non-covalent bonds can result in impressive modifications of the metallo-supramolecular structure and, subsequently, produces changes in the properties of the designed material. The present feature article provides an overview on recent developments in the field of metallo-polymerization of chelating terpyridyl and analogues ligands. Synthetic strategies are described followed by a discussion regarding the characterization and the application of the reviewed metallo-supramolecular structures, mainly based on terpyridines.

International audience; Superparamagnetic iron oxide nanoparticles (SPIONs) are recognized to be an attractive platform for developing novel drug delivery approaches and thus several types of functionalized magnetic nanocarriers based on SPIONs have been synthesized and studied. The coating of the metal oxide surface was achieved in a one-pot synthesis with biocompatible polyethylene glycol (PEG) and thermo-responsive modified Pluronic® F68. The resulting thermo-responsive magnetic nanocarriers can incorporate water insoluble drugs into their hydrophobic compartment and later release them in a temperature dependent manner. Here we report novel magnetic nanocarriers with significant improvements regarding the colloidal stability and critical temperature obtained by mixing various molar ratios of hydrophilic PEG with thermo-responsive Pluronic® F68 bearing different end group functionalities. Various methods have been employed to characterize the magnetic nanocarriers, such as photon correlation spectroscopy (DLS), atomic absorption, FT-IR spectroscopy, and surface-enhanced Raman scattering. The transition temperature that determines changes in the conformation of the block copolymer chain was studied by DLS as a function of temperature. Moreover, the drug loading properties of SPION-(F68-OMe)-(F68-FA) and SPION-PEG-F68-FA were analyzed with a hydrophobic fluorescent dye, DID oil. The behavior of the encapsulated DID into the nanocarrier shell was studied as a function of temperature via fluorescence spectroscopy. These results offer original insights into the enhanced colloidal stability and thermo-sensitive properties of the novel synthesized magnetic nanocarriers.

In order to obtain linear and high molecular weight Ru(II) coordination polymers, we investigated the reaction conditions for the direct one-step metallopolymerization of bis-terpyridine poly(ethylene glycol) 3 with RuCl3 in the presence of reducing agents. Here we discuss the direct synthesis method, the optimization and the purification of the water soluble Ru(II) chain extended poly(ethylene glycol). The optimization of the metallo-polymerization was monitored by SEC. For the highest molecular weight Ru(II) coordination polymer 4 obtained in this study, full characterization was performed by 1H-NMR and UV-Vis spectroscopy as well as SEC proof for the formation and the stability of the designed structure