Persistent luminescence nanoparticles functionalized by polymers bearing phosphonic acid anchors: synthesis, characterization, and in vivo behaviour.

Optical in vivo imaging has become a widely used technique and is still under development for clinical diagnostics and treatment applications. For further development of the field, researchers have put much effort into the development of inorganic nanoparticles (NPs) as imaging probes. In this trend, our laboratory developed ZnGa1.995O4Cr0.005 (ZGO) nanoparticles, which can emit a bright persistent luminescence signal through the tissue transparency window for dozens of minutes and can be activated in vivo with visible irradiation. These properties endow them with unique features, allowing us to recover information over a long-time study with in vivo imaging without any background. To target tissues of interest, ZGO must circulate long enough in the blood stream, a phenomenon which is limited by the mononuclear phagocyte system (MPS). Depending on their size, charge and coating, the NPs are sooner or later opsonized and stored into the main organs of the MPS (liver, spleen, and lungs). The NPs therefore have to be coated with a hydrophilic polymer to avoid this limitation. To this end, a new functionalization method using two different polyethylene glycol phosphonic acid polymers (a linear one, later named lpPEG and a branched one, later named pPEG) has been studied in this article. The coating has been optimized and characterized in various aqueous media. The behaviour of the newly functionalized NPs has been investigated in the presence of plasmatic proteins, and an in vivo biodistribution study has been performed. Among them ZGOpPEG exhibits a long circulation time, corresponding to low protein adsorption, while presenting an effective one-step process in aqueous medium with a low hydrodynamic diameter increase. This new method is much more advantageous than another strategy we reported previously that used a two-step PEG silane coating performed in an organic solvent (dimethylformamide) for which the final hydrodynamic diameter was twice the initial diameter.

Antioxidant Activity and Toxicity Study of Cerium Oxide Nanoparticles Stabilized with Innovative Functional Copolymers.

Oxidative stress, which is one of the main harmful mechanisms of pathologies including ischemic stroke, contributes to both neurons and endothelial cell damages, leading to vascular lesions. Although many antioxidants are tested in preclinical studies, no treatment is currently available for stroke patients. Since cerium oxide nanoparticles (CNPs) exhibit remarkable antioxidant capacities, the objective is to develop an innovative coating to enhance CNPs biocompatibility without disrupting their antioxidant capacities or enhance their toxicity. This study reports the synthesis and characterization of functional polymers and their impact on the enzyme-like catalytic activity of CNPs. To study the toxicity and the antioxidant properties of CNPs for stroke and particularly endothelial damages, in vitro studies are conducted on a cerebral endothelial cell line (bEnd.3). Despite their internalization in bEnd.3 cells, coated CNPs are devoid of cytotoxicity. Microscopy studies report an intracellular localization of CNPs, more precisely in endosomes. All CNPs reduces glutamate-induced intracellular production of reactive oxygen species (ROS) in endothelial cells but one CNP significantly reduces both the production of mitochondrial superoxide anion and DNA oxidation. In vivo studies report a lack of toxicity in mice. This study therefore describes and identifies biocompatible CNPs with interesting antioxidant properties for ischemic stroke and related pathologies.

Polymer-Coated Cerium Oxide Nanoparticles as Oxidoreductase-like Catalysts.

Cerium oxide nanoparticles have been shown to mimic oxidoreductase enzymes by catalyzing the decomposition of organic substrates and reactive oxygen species. This mimicry can be found in superoxide radicals and hydrogen peroxides, which are harmful molecules produced in oxidative stress-associated diseases. Despite the fact that nanoparticle functionalization is mandatory in the context of nanomedicine, the influence of polymer coatings on their enzyme-like catalytic activity is poorly understood. In this work, six polymer-coated cerium oxide nanoparticles are prepared by the association of 7.8 nm cerium oxide cores with two poly(sodium acrylate) and four poly(ethylene glycol) (PEG)-grafted copolymers with different terminal or anchoring end groups, such as phosphonic acids. The superoxide dismutase-, catalase-, peroxidase-, and oxidase-like catalytic activities of the coated nanoparticles were systematically studied. It is shown that the polymer coatings do not affect the superoxide dismutase-like, impair the catalase-like and oxidase-like, and surprisingly improves peroxidase-like catalytic activities of cerium oxide nanoparticles. It is also demonstrated that the particles coated with the PEG-grafted copolymers perform better than the poly(acrylic acid)-coated ones as oxidoreductase-like enzymes, a result that confirms the benefit of having phosphonic acids as anchoring groups at the particle surface.

Prebiotic synthesis of 2-deoxy-d-ribose from interstellar building blocks promoted by amino esters or amino nitriles.

Understanding the prebiotic genesis of 2-deoxy-d-ribose, which forms the backbone of DNA, is of crucial importance to unravelling the origins of life, yet remains open to debate. Here we demonstrate that 20 mol% of proteinogenic amino esters promote the selective formation of 2-deoxy-d-ribose over 2-deoxy-d-threopentose in combined yields of ≥4%. We also demonstrate the first aldol reaction promoted by prebiotically-relevant proteinogenic amino nitriles (20 mol%) for the enantioselective synthesis of d-glyceraldehyde with 6% ee, and its subsequent conversion into 2-deoxy-d-ribose in yields of ≥ 5%. Finally, we explore the combination of these two steps in a one-pot process using 20 mol% of an amino ester or amino nitrile promoter. It is hence demonstrated that three interstellar starting materials, when mixed together with an appropriate promoter, can directly lead to the formation of a mixture of higher carbohydrates, including 2-deoxy-d-ribose.

Serum Protein-Resistant Behavior of Multisite-Bound Poly(ethylene glycol) Chains on Iron Oxide Surfaces.

Recent surveys have shown that the number of nanoparticle-based formulations actually used at a clinical level is significantly lower than that expected a decade ago. One reason for this is that the physicochemical properties of nanoparticles fall short for handling the complexity of biological environments and preventing nonspecific protein adsorption. In this study, we address the issue of the interactions of plasma proteins with polymer-coated surfaces. With this aim, we use a noncovalent grafting-to method to functionalize iron oxide sub-10 nm nanoparticles and iron oxide flat substrates and compare their protein responses. The functionalized copolymers consist of alternating poly(ethylene glycol) (PEG) chains and phosphonic acid grafted on the same backbone. Quartz crystal microbalance with dissipation was used to monitor polymer adsorption kinetics and evaluate the resistance to protein adsorption. On flat substrates, functionalized PEG copolymers adsorb and form a brush in moderate or highly stretched regimes, with densities between 0.15 and 1.5 nm-2. PEG layers using phosphonic acid as linkers exhibit excellent protein resistance. In contrast, layers prepared with carboxylic acid as the grafting agent exhibit mitigated protein responses and layer destructuration. The present study establishes a correlation between the long-term stability of PEG-coated particles in biofluids and the protein resistance of surfaces coated with the same polymers.