Combined magnetic resonance imaging and photodynamic therapy using polyfunctionalised nanoparticles bearing robust gadolinium surface units

A robust dithiocarbamate tether allows novel gadolinium units based on DOTAGA (q = 1) to be attached to the surface of gold nanoparticles (2.6 ‐ 4.1 nm diameter) along with functional units offering biocompatibility, targeting and photodynamic therapy. A dramatic increase in relaxivity (r1) per Gd unit from 5.01 mM−1 s−1 in unbound form to 31.68 mM−1 s−1 (10 MHz, 37 °C) is observed when immobilised on the surface due to restricted rotation and enhanced rigidity of the Gd complex on the nanoparticle surface. The single‐step synthetic route provides a straightforward and versatile way of preparing multifunctional gold nanoparticles, including examples with conjugated zinc‐tetraphenylporphyrin photosensitizers. The lack of toxicity of these materials (MTT assays) is transformed on irradiation of HeLa cells for 30 minutes (PDT), leading to 75% cell death. In addition to passive targeting, the inclusion of units capable of actively targeting overexpressed folate receptors illustrates the potential of these assemblies as targeted theranostic agents

Polyfunctionalised nanoparticles bearing robust gadolinium surface units for high relaxivity performance in MRI

The first example of an octadentate gadolinium unit based on DO3A (hydration number q = 1) with a dithiocarbamate tether has been designed and attached to the surface of gold nanoparticles (around 4.4 nm in diameter). In addition to the superior robustness of this attachment, the restricted rotation of the Gd complex on the nanoparticle surface leads to a dramatic increase in relaxivity (r1) from 4.0 mM‐1 s‐1 in unbound form to 34.3 mM‐1 s‐1 (at 10 MHz, 37 °C) and 22 ± 2 mM‐1s‐1 (at 63.87 MHz, 25 °C) when immobilised on the surface. The ‘one‐pot’ synthetic route provides a straightforward and versatile way of preparing a range of multifunctional gold nanoparticles. The incorporation of additional surface units improving biocompatibility (PEG and thioglucose units) and targeting (folic acid) lead to little detrimental effect on the high relaxivity observed for these non‐toxic multifunctional materials. In addition to the passive targeting attributed to gold nanoparticles, the inclusion of a unit capable of targeting the folate receptors overexpressed by cancer cells, such as HeLa cells, illustrates the potential of these assemblies

Prediction of second neurological attack in patients with clinically isolated syndrome using support vector machines

The aim of this study is to predict the conversion from clinically isolated syndrome to clinically definite multiple sclerosis using support vector machines. The two groups of converters and non-converters are classified using features that were calculated from baseline data of 73 patients. The data consists of standard magnetic resonance images, binary lesion masks, and clinical and demographic information. 15 features were calculated and all combinations of them were iteratively tested for their predictive capacity using polynomial kernels and radial basis functions with leave-one-out cross-validation. The accuracy of this prediction is up to 86.4% with a sensitivity and specificity in the same range indicating that this is a feasible approach for the prediction of a second clinical attack in patients with clinically isolated syndromes, and that the chosen features are appropriate. The two features gender and location of onset lesions have been used in all feature combinations leading to a high accuracy suggesting that they are highly predictive. However, it is necessary to add supporting features to maximise the accuracy. © 2013 IEEE

Functionalised gold nanoparticles for theranostics

New contrast agents based on the DO3A and DOTAGA moieties can be synthesised and attached to the surface of small spherical gold nanoparticles, with a core diameter of around 2-4 nm. This is achieved through the use of a dithiocarbamate tether to robustly anchor these complexes to the surface. In addition to the stronger attachment to the nanoparticles, the dithiocarbamate severely reduces the rotation of the paramagnetic species. This restriction of rotation is further optimised through the use of a piperazine linker that enforces a ‘double locking’ mechanism, through the amide and the dithiocarbamate. The DO3A derivative is first described in Chapter 2, in which its synthesis, stability towards transmetallation and relaxivity are investigated. It is revealed that the compound can be synthesised in a relatively large scale (>1g) and has an extremely good stability, as almost no transmetallation occurs after 45h even in the presence of 10 equivalents of zinc. The compound forms complexes with three separate metals to generate mono-, bi- and tri-gadolinium species which produce up to a 6.5-fold increase in the overall relaxivity for the tri-gadolinium complex. Both new contrast agents are anchored to the surface of gold nanoparticles through a straightforward ‘one-pot’ synthetic route, generating stable and monodisperse particles. A dramatic boost in relaxivity is achieved through this attachment, from 4.5 mM-1 s-1 to 34.3 mM-1 s-1 for the first generation surface units and 5.0 mM-1 s-1 to 31.7 mM-1 s-1, at 10 MHz and 37 ºC. The incorporation of additional surface units, to achieve a stealth character (PEG), higher cellular uptake (thioglucose) and targeting (folic acid), is achieved in a straightforward and flexible way utilising the same ‘one-pot’ synthetic route. These additional surface units display little negative impact on the relaxivity or stability of these non-cytotoxic particles. Increased cellular uptake occurs when these surface units are combined and the cellular internalisation behaviour is confirmed through the use of a BODIPY derivative. The use of a lipoic acid derivative of a zinc porphyrin allows the addition of photodynamic therapy (PDT) to the assembly. In the absence of light, no cytotoxicity is noted with these nanoparticles but close to 80% cell death is achieved after only 30 min irradiation with a laser. The relaxivity of these particles at high magnetic field (127.8 MHz) is 1.5-fold higher than that of commercially utilised Dotarem®, making these non-cytotoxic, theranostic agents suitable for in vivo investigations.Open Acces

BiodivAR: ::a cartographic authoring tool for the visualization of geolocated media in augmented reality

Location-based augmented reality technology for real-world, outdoor experiences is rapidly gaining in popularity in a variety of fields such as engineering, education, and gaming. By anchoring medias to geographic coordinates, it is possible to design immersive experiences remotely, without necessitating an in-depth knowledge of the context. However, the creation of such experiences typically requires complex programming tools that are beyond the reach of mainstream users. We introduce BiodivAR, a web cartographic tool for the authoring of location-based AR experiences. Developed using a user-centered design methodology and open-source interoperable web technologies, it is the second iteration of an effort that started in 2016. It is designed to meet needs defined through use cases co-designed with end users and enables the creation of custom geolocated points of interest. This approach enabled substantial progress over the previous iteration. Its reliance on geolocation data to anchor augmented objects relative to the user’s position poses a set of challenges: On mobile devices, GNSS accuracy typically lies between 1 m and 30 m. Due to its impact on the anchoring, this lack of accuracy can have deleterious effects on usability. We conducted a comparative user test using the application in combination with two different geolocation data types (GNSS versus RTK). While the test’s results are undergoing analysis, we hereby present a methodology for the assessment of our system’s usability based on the use of eye-tracking devices, geolocated traces and events, and usability questionnaires

Metallostar assemblies based on dithiocarbamates for use as MRI contrast agents

Two different octadentate gadolinium chelates based on DO3A and DOTAGA chelates (hydration number q = 1) have been used to prepare a series of bi-, tri-, and tetrametallic d–f mixed-metal complexes. The piperazine-based dithiocarbamate linker ensures that rotation of the gadolinium chelates is restricted, leading to enhanced relaxivity (r1) values, which increase with the overall mass and number of gadolinium units. The r1 value (at 10 MHz, 25 °C) per gadolinium unit rises from 5.0 mM–1 s–1 for the Gd-DO3A-NH2 monogadolinium chelate to 9.2 mM–1 s–1 in a trigadolinium complex with a ruthenium(III) core. Using a 1.5 T clinical scanner operating at 63.87 MHz (25 °C), an 86% increase in the relaxivity per gadolinium unit is observed for this multimetallic compound compared to clinically approved Dotarem. The gadolinium complexes based on the DOTAGA chelate also performed well at 63.87 MHz, with a relaxivity value of 9.5 mM–1 s–1 per gadolinium unit being observed for the trigadolinium d–f mixed-metal complex with a ruthenium(III) core. The versatility of dithiocarbamate coordination chemistry thus provides access to a wide range of d–f hybrids with potential for use as high-performance MRI contrast agents

Artefact : enjeux de formation

International audienceLa notion d’artefact désigne aussi bien un objet qu’un système artificiel pour peu qu’il soit conçu, fabriqué et utilisé par l’être humain. Par son caractère pluridisciplinaire, l’artefact facilite l’ouverture des dialogues entre chercheurs. Ces points de vue diversifiés et contrastés génèrent une grande variété de définitions. Dans cette logique, cet ouvrage collectif propose des regards pluriels sur les artefacts convoqués au sein des actions de formation.Sa dimension transversale offre de nouveaux terrains d’investigations particulièrement féconds pour les recherches en éducation. Par sa spécificité à cristalliser l’activité humaine, l’artefact amène les acteurs de la formation, concepteurs ou usagers, à accéder à la densité des savoirs qu’il contient et qu’il présuppose