Tunable Naphthalimide/Cinnoline‐Fused (CinNapht) Hybrid Dyes for Fluorescence Imaging in Living Cells

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A Facile One-Pot Synthesis of Versatile PEGylated Platinum Nanoflowers and Their Application in Radiation Therapy

International audienceNanomedicine has stepped into the spotlight of radiation therapy over the last two decades. Nanoparticles (NPs), especially metallic NPs, can potentiate radiotherapy by specific accumulation into tumors, thus enhancing the efficacy while alleviating the toxicity of radiotherapy. Water radiolysis is a simple, fast and environmentally-friendly method to prepare highly controllable metallic nanoparticles in large scale. In this study, we used this method to prepare biocompatible PEGylated (with Poly(Ethylene Glycol) diamine) platinum nanoflowers (Pt NFs). These nanoagents provide unique surface chemistry, which allows functionalization with various molecules such as fluorescent markers, drugs or radionuclides. The Pt NFs were produced with a controlled aggregation of small Pt subunits through a combination of grafted polymers and radiation-induced polymer cross-linking. Confocal microscopy and fluorescence lifetime imaging microscopy revealed that Pt NFs were localized in the cytoplasm of cervical cancer cells (HeLa) but not in the nucleus. Clonogenic assays revealed that Pt NFs amplify the gamma rays induced killing of HeLa cells with a sensitizing enhancement ratio (SER) of 23%, thus making them promising candidates for future cancer radiation therapy. Furthermore, the efficiency of Pt NFs to induce nanoscopic biomolecular damage by interacting with gamma rays, was evaluated using plasmids as molecular probe. These findings show that the Pt NFs are efficient nano-radio-enhancers. Finally, these NFs could be used to improve not only the performances of radiation therapy treatments but also drug delivery and/or diagnosis when functionalized with various molecules

“CinNapht” Dyes as New Cinnoline/Naphthalimide Fused Hybrids Fluorophores: Synthesis, Photo-Physical Study and Use for Bio-Imaging

Six-membered diaza ring of Cinnoline have been fused on Naphthalimide dye to give donor–acceptor system called CinNapht. These red shifted fluorophore, that can be synthetised in gram scale, exhibits a large Stoke Shift and quantum yield up to 0.33. It is also caracterized by strong solvatochromic effect for green to red emission as well and can be used for bio-imagin

Pharmacokinetics derived from PET imaging of inspiring radio-enhancer platinum nanoparticles

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A customized long acting formulation of the kisspeptin analog C6 triggers ovulation in anestrus ewe

International audienceThe modulation of the kisspeptin system holds promise as a treatment for human reproductive disorders and for managing livestock breeding. The design of analogs has overcome some unfavorable properties of the endogenous ligands. However, for applications requiring a prolongation of drug activity, such as ovulation induction in the ewe during the non-breeding season, additional improvement is required. To this aim, we designed and tested three formulations containing the kisspeptin analog C6. Two were based on polymeric nanoparticles (NP1 and NP2) and the third was based on hydrogels composed of a mixture of cyclodextrin polymers and dextran grafted with alkyl side chains (MD/pCD). Only the MD/pCD formulation prolonged C6 activity, as shown by monitoring luteinizing hormone (LH) plasma concentration (elevation duration 23.4 +/- 6.1, 13.7 +/- 4.7 and 12.0 +/- 2.4 h for MD/pCD, NP1 and NP2, respectively). When compared with the free C6 (15 nmol/ewe), the formulated (MD/pCD) doses of 10, 15 and 30 nmol/ewe, but not the 90 nmol/ewe dose, provided a more gradual release of C6 as shown by an attenuated LH release during the first 6 h post-treatment. When tested during the non-breeding season without progestogen priming, only, the formulated 30 nmol/ewe dose triggered ovulation (50% of ewes). Hence, we showed that a formulation with an adapted action time would improve the efficacy of C6 with respect to inducing ovulation during the non-breeding season. This result suggests that formulations containing a kisspeptin analog might find applications in the management of livestock reproduction but also point to the possibility of their use for the treatment of some human reproductive pathologies

Green One-Step Synthesis of Medical Nanoagents for Advanced Radiation Therapy

Purpose: Metal-based nanoparticles (M-NPs) have attracted great attention in nanomedicine due to their capacity to amplify and improve the tumor targeting of medical beams. However, their simple, efficient, high-yield and reproducible production remains a challenge. Currently, M-NPs are mainly synthesized by chemical methods or radiolysis using toxic reactants. The waste of time, loss of material and potential environmental hazards are major limitations.Materials and Methods: This work proposes a simple, fast and green strategy to synthesize small, non-toxic and stable NPs in water with a 100% production rate. Ionizing radiation is used to simultaneously synthesize and sterilize the containing NPs solutions. The synthesis of platinum nanoparticles (Pt NPs) coated with biocompatible poly(ethylene glycol) ligands (PEG) is presented as proof of concept. The physicochemical properties of NPs were studied by complementary specialized techniques. Their toxicity and radio-enhancing properties were evaluated in a cancerous in vitro model. Using plasmid nanoprobes, we investigated the elementary mechanisms underpinning radio-enhancement.Results and Discussion: Pt NPs showed nearly spherical-like shapes and an average hydrodynamic diameter of 9 nm. NPs are zero-valent platinum successfully coated with PEG. They were found non-toxic and have the singular property of amplifying cell killing induced by γ-rays (14%) and even more, the effects of carbon ions (44%) used in particle therapy. They induce nanosized-molecular damage, which is a major finding to potentially implement this protocol in treatment planning simulations.Conclusion: This new eco-friendly, fast and simple proposed method opens a new era of engineering water-soluble biocompatible NPs and boosts the development of NP-aided radiation therapies

<p>Green One-Step Synthesis of Medical Nanoagents for Advanced Radiation Therapy</p>

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Étonnante physique

International audienceDiscipline multimillénaire, la physique explore l’espace et le temps. De l’immensité des amas de galaxies à l’infinie petitesse des particules élémentaires, des échelles humaines – du mètre au centimètre – jusqu’au nanomonde, de l’extrême brièveté du mouvement de l’électron jusqu’au fond des âges d’où nous parviennent les premières lumières de l’Univers : les domaines couverts par cette discipline n’ont pas fini de nous étonner.Cette science est celle de l’expérimentation méthodique qui met au point des instruments originaux pour observer la matière, inerte ou vivante, en laboratoire ou à distance. Celle qui pose encore de grandes questions fondamentales. Mais aussi celle qui accompagne notre vie quotidienne avec ses développements dans les domaines des matériaux, de la santé, de l’énergie, du climat…Pour montrer toute sa richesse, cet ouvrage réunit 70 contributions de physiciennes et de physiciens récemment récompensés par une médaille du CNRS pour l’originalité et l’importance de leurs travaux. Abondamment illustré, accessible à tout amateur de science, Étonnante Physique lève un voile sur les recherches les plus actuelles