AGuIX® from bench to bedside-Transfer of an ultrasmall theranostic gadolinium-based nanoparticle to clinical medicine

International audienceAGuIX® are sub-5 nm nanoparticles made of a polysiloxane matrix and gadolinium chelates. This nanoparticle has been recently accepted in clinical trials in association with radiotherapy. This review will summarize the principal preclinical results that have led to first in man administration. No evidence of toxicity has been observed during regulatory toxicity tests on two animal species (rodents and monkeys). Biodistributions on different animal models have shown passive uptake in tumours due to enhanced permeability and retention effect combined with renal elimination of the nanoparticles after intravenous administration. High radiosensitizing effect has been observed with different types of irradiations in vitro and in vivo on a large number of cancer types (brain, lung, melanoma, head and neck…). The review concludes with the second generation of AGuIX nanoparticles and the first preliminary results on human

Site-Specific Anchoring of a Flavonol Dye into Zeolite β Nanoparticles

International audienceThe structural and electronic properties of the accessible CuI site of a faujasite-type zeolite have been studied, by use of large cluster models and a density functional theory-based methodology. We demonstrate that the local ideal C3 symmetry of the CuI site II is broken. The CuI cation is bonded to the zeolite framework by one bond of about 2.26 Å and two shorter ones of 2.07 Å. We demonstrate that only one cation position exists at this site. This result is also confirmed by a molecular electrostatic potential analysis. We show that local properties at site II, as well as the global properties of the solid (frontier orbitals), do not depend on the Al and cation distribution and only slightly on the cocation nature. Taking into account the present results and well-known experimental data, we propose that specific catalytic behaviors are correlated with local response properties, such as the local acid strength or, in other reactions, specific local architecture or confinement

Multiphoton dissociation of macromolecular ions at the single-molecule level

International audienceThe laser-induced decay of ethylene oxide polymer ions of megadalton size has been studied in the multiphoton IR excitation regime, with fragmentation products of individual ions being monitored over long times by a trapping device. The experiment reveals several fragmentation pathways having distinct signatures at the single-molecule level that would not be accessible from studies based on statistically averaged reaction rates only. The observations are supported by dedicated molecular simulations based on a coarse-grained model, which further highlight the role played by continuous heating in such out-of-equilibrium conditions. In particular, both experiment and modeling indicate that the dissociation kinetics depends nonlinearly on heating rate

Multiphoton Dissociation of Electrosprayed MegaDalton-Sized DNA Ions in a Charge-Detection Mass Spectrometer

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Pushing the Limit of Infrared Multiphoton Dissociation to Megadalton-Size DNA Ions

International audienceWe report the use of infrared multiphoton dissociation (IRMPD) for the determination of relative activation energies for unimolecular dissociation of megadalton DNA ions. Single ions with masses in the megadalton range were stored in an electrostatic ion trap for a few tens of milliseconds and the image current generated by the roundtrips of ions in the trap was recorded. While being trapped, single ions were irradiated by a CO2 laser and fragmented, owing to multiphoton IR activation. The analysis of the single-ion image current during the heating period allows us to measure changes in the charge of the trapped ion. We estimated the activation energy associated with the dissociation of megadalton-size DNA ions in the frame of an Arrhenius-like model by analyzing a large set of individual ions in order to construct a frequency histogram of the dissociation rates for a collection of ions

Flavonol dye molecules in zeolite beta nanocrystals for biodiagnostic applications

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Direct determination of molecular weight distribution of calf‐thymus DNAs and study of their fragmentation under ultrasonic and low‐energy infrared irradiations. A charge detection mass spectrometry investigation

International audienceRationaleCalf‐thymus (CT‐DNA) is widely used as a binding agent. The commercial samples are known to be “highly polymerized DNA” samples. CT‐DNA is known to be fragile in particular upon ultrasonic wave irradiation. Degradation products could have dramatic consequences on its bio‐sensing activity, and an accurate determination of the molecular weight distribution and stability of commercial samples is highly demanded.MethodsWe investigated the sensitivity of charge detection mass spectrometry (CDMS), a single‐molecule MS method, both with single‐pass and ion trap CDMS (“Benner” trap) modes to the determination of the composition and stability (under multiphoton IR irradiation) of calf‐thymus DNAs. We also investigated the changes in molecular weight distributions in the course of sonication by irradiating ultrasonic waves to CT‐DNA.ResultsWe report, for the first time, the direct molecular weight (MW) distribution of DNA sodium salt from calf‐thymus revealing two populations at high (~10 MDa) and low (~3 MDa) molecular weights. We evidence a transition between the high‐MW to the low‐MW distribution, confirming that the low‐MW distribution results from degradation of CT‐DNA. Finally, we report also IRMPD experiments carried out on trapped single‐stranded linear DNAs from calf‐thymus allowing extraction of their activation energy for unimolecular dissociation.ConclusionsWe show that single‐pass CDMS is a direct, efficient and accurate MS‐based approach to determine the composition of calf‐thymus DNAs. Furthermore, ion trap CDMS allows us to evaluate the stability (both under multiphoton IR irradiation and in the course of sonication by irradiating ultrasonic wave) of calf‐thymus DNAs

Synthesis of Phosphonic Acids with the Semicarbazide Group for the Functionalization of Metal Oxide and Zeolite Nanoparticles

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Correlation between the charge of polymer particles in solution and in the gas phase investigated by zeta-potential measurements and electrospray ionization mass spectrometry.

International audienceThe relationship between the effective charge of polymer nanoparticles (PNP) in solution and the charge states of ionized particles produced in the gas phase by electrospray ionization was investigated. Charge detection mass spectrometry was used to measure both the mass and charge of individual electrosprayed ions. The effective charges extracted from the measured zeta-potential of PNPs in solution are partially correlated with the average values of charge of PNPs in the gas phase. The correlation between the magnitude of charging of PNPs ions produced in the gas phase with the PNPs surface charge in solution demonstrates that the mass spectrometry-based analysis described in this work is an alternative and promising way for a fast and systematic characterization of charges on colloidal particles