Synthesis, electron tomography and single-particle optical response of twisted gold nano-bipyramids

International audienceA great number of works focus their interest on the study of gold nanoparticle plasmonic properties. Among those, sharp nanostructures appear to exhibit the more interesting features for further developments. In this paper, a complete study on bipyramidal-like gold nanostructures is presented. The nano-objects are prepared in high yield using an original method. This chemical process enables a precise control of the shape and the size of the particles. The specific photophysical properties of gold bipyramids in suspension are ripened by recording the plasmonic response of single and isolated objects. Resulting extinction spectra are precisely correlated to their geometrical structure by mean of electron tomography at the single-particle level. The interplay between the geometrical structure and the optical properties of twisted gold bipyramids is further discussed on the basis of numerical calculations. The influence of several parameters is explored such as the structural aspect ratio or the tip truncation. In the case of an incident excitation polarized along the particle long axis, this study shows how the plasmon resonance position can be sensitive to these parameters and how it can then be efficiently tuned on a large wavelength range

Liquid-Crystalline Suspensions of Photosensitive Paramagnetic CeF 3 Nanodiscs

International audienceThe design of high-performance energy-converting materials is an essential step for the development of sensors, but the production of the bulk materials currently used remains costly and difficult. Therefore, a different approach based on the self-assembly of nanoparticles has been explored. We report on the preparation by solvothermal synthesis of highly crystalline CeF 3 nanodiscs. Their surface modification by bisphosphonate ligands led to stable, highly concentrated, colloidal suspensions in water. Despite the low aspect ratio of the nanodiscs (∼6), a liquidcrystalline nematic phase spontaneously appeared in these colloidal suspensions. Thanks to the paramagnetic character of the nanodiscs, the nematic phase was easily aligned by a weak (0.5 T) magnetic field, which provides a simple and convenient way of orienting all of the nanodiscs in suspension in the same direction. Moreover, the more dilute, isotropic, suspensions displayed strong (electric and magnetic) fieldinduced orientation of the nanodiscs (Kerr and Cotton−Mouton effects), with fast enough response times to make them suitable for use in electro-optic devices. Furthermore, an emission study showed a direct relation between the luminescence intensity and magnetic-field-induced orientation of the colloids. Finally, with their fast radiative recombination decay rates, the nanodiscs show luminescence properties that compare quite favorably with those of bulk CeF 3. Therefore, these CeF 3 nanodiscs are very promising building blocks for the development and processing of photosensitive materials for sensor applications

Radiation Dose-Enhancement Is a Potent Radiotherapeutic Effect of Rare-Earth Composite Nanoscintillators in Preclinical Models of Glioblastoma

International audienceTo improve the prognosis of glioblastoma, innovative radiotherapy regimens are required to augment the effect of tolerable radiation doses while sparing surrounding tissues. In this context, nanoscintillators are emerging radiotherapeutics that down‐convert X‐rays into photons with energies ranging from UV to near‐infrared. During radiotherapy, these scintillating properties amplify radiation‐induced damage by UV‐C emission or photodynamic effects. Additionally, nanoscintillators that contain high‐Z elements are likely to induce another, currently unexplored effect: radiation dose‐enhancement. This phenomenon stems from a higher photoelectric absorption of orthovoltage X‐rays by high‐Z elements compared to tissues, resulting in increased production of tissue‐damaging photo‐ and Auger electrons. In this study, Geant4 simulations reveal that rare‐earth composite LaF3:Ce nanoscintillators effectively generate photo‐ and Auger‐electrons upon orthovoltage X‐rays. 3D spatially resolved X‐ray fluorescence microtomography shows that LaF3:Ce highly concentrates in microtumors and enhances radiotherapy in an X‐ray energy‐dependent manner. In an aggressive syngeneic model of orthotopic glioblastoma, intracerebral injection of LaF3:Ce is well tolerated and achieves complete tumor remission in 15% of the subjects receiving monochromatic synchrotron radiotherapy. This study provides unequivocal evidence for radiation dose‐enhancement by nanoscintillators, eliciting a prominent radiotherapeutic effect. Altogether, nanoscintillators have invaluable properties for enhancing the focal damage of radiotherapy in glioblastoma and other radioresistant cancers

Hybrid Multimodal Contrast Agent for Multiscale In Vivo Investigation of Neuroinflammation

International audienceNeuroinflammation is a process common to several brain pathologies. Despites its medical relevance, it still remains poorly understood; there is therefore a need to develop new in vivo imaging strategies to monitor inflammatory processes longitudinally. We here present the development of a hybrid imaging nanoprobe named NP3, that was specifically designed to get internalized by phagocytic cells and imaged in vivo with MRI and bi-photon microscopy. NP3 is composed of a 16 nm core of gadolinium fluoride (GdF3), coated with bisphosphonate polyethylene glycol (PEG) and functionalized with a Lemke-type fluorophore (LEM-A). It has a hydrodynamic diameter of 28±8 nm and a zeta potential of-42±6 mV. The MR relaxivity ratio at 7T is r1/r2 = 20; therefore, NP3 is well suited as a T2/T2* contrast agent. In vitro cytotoxicity assessments performed on four human cell lines revealed no toxic effects of NP3. In addition, NP3 is internalized by macrophages in vitro without inducing inflammation or cytotoxicity. In vivo, uptake of NP3 has been observed in the spleen and the liver. NP3 has a prolonged vascular remanence, which is an advantage for macrophage uptake in vivo. The proof-of-concept that NP3 may be used as a contrast agent targeting phagocytic cells is provided in an animal model of ischemic stroke in transgenic CX3CR1-GFP/+ mice using three complementary imaging modalities: MRI, intravital two-photon microscopy and phase contrast imaging with synchrotron X-rays. In summary, 2 NP3 is a promising preclinical tool for the multiscale and multimodal investigation of neuroinflammation

Multimodal Imaging with NanoGd Reveals Spatiotemporal Features of Neuroinflammation after Experimental Stroke

International audienceThe purpose of this study is to propose and validate a preclinical in vivo magnetic resonance imaging (MRI) tool to monitor neuroinflammation following ischemic stroke, based on injection of a novel multimodal nanoprobe, NanoGd, specifically designed for internalization by phagocytic cells. First, it is verified that NanoGd is efficiently internalized by microglia in vitro. In vivo MRI coupled with intravenous injection of NanoGd in a permanent middle cerebral artery occlusion mouse model results in hypointense signals in the ischemic lesion. In these mice, longitudinal two-photon intravital microscopy shows NanoGd internalization by activated CX3CR1-GFP/+ cells. Ex vivo analysis, including phase contrast imaging with synchrotron X-ray, histochemistry, and transmission electron microscopy corroborate NanoGd accumulation within the ischemic lesion and uptake by immune phagocytic cells. Taken together, these results confirm the potential of NanoGd-enhanced MRI as an imaging biomarker of neuroinflammation at the subacute stage of ischemic stroke. As far as it is known, this work is the first to decipher the working mechanism of MR signals induced by a nanoparticle passively targeted at phagocytic cells by performing intravital microscopy back-to-back with MRI. Furthermore, using a gadolinium-based rather than an iron-based contrast agent raises future perspectives for the development of molecular imaging with emerging computed tomography technologies