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Xavier Le Guével

Xavier Le Guével
University Grenoble-Alpes · IAB, INSERM-U1209 / CNRS-UMR 5309

PhD

About

69
Publications
15,327
Reads
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2,270
Citations
Introduction
My main research activities are related to the development of engineered nanoparticles and nanostructures for biomedical applications such as cancer therapy & diagnostic and to the use of in vivo optical imaging systems.
Additional affiliations
January 2016 - present
University Grenoble-Alpes
Position
  • CNRS Researcher
January 2012 - present
Centro Andaluz de Nanomedicina y Biotecnología
Position
  • Researcher
January 2010 - January 2012
Universität des Saarlandes
Position
  • Senior Researcher
Description
  • Study of fluorescent noble metal nanoclusters for life imaging and sensing - Development of nanocomposites for antibacterial and pharmaceutical applications

Publications

Publications (69)
Article
Full-text available
Understanding how ultra-small gold nanoparticles (metal core ~ 1–1.5 nm), so-called gold nanoclusters (Au NCs), interact with biological barriers has become highly important for their future bioapplications. The properties of Au NCs with tunable hydrophobicity were extensively characterized in 3 different biological situations: i) interaction with...
Article
Full-text available
In parallel with the rapidly growing and widespread use of nanomedicine in the clinic, we are also witnessing the development of so-called theranostic agents that combine diagnostic and therapeutic properties. Among them, ultra-small gold nanoclusters (Au NCs) are showing promising potential due to their optical properties and activatable therapeut...
Article
We synthesized a generation of water-soluble, atomically precise gold nanoclusters (Au NCs) with anisotropic surface containing short dithiol pegylated chain (AuMHA/TDT). These AuMHA/TDT exhibit a high brightness (QY∼6%) in the shortwave infrared (SWIR) spectrum with a detection above 1250 nm. Furthermore, they show an extended half-life in blood (...
Cover Page
Full-text available
The antibacterial action of large (>10 nm) spherical gold nanoparticles is demonstrated by Elena P. Ivanova and co‐workers in article number 2005679 to be attributed to the combined stretching and rupture of the bacterial cell membrane. The newly discovered mechanical modes of antibacterial action pose varied implications for the use and applicatio...
Cover Page
Full-text available
A detailed description of photophysical properties of NIR-II emitting probe and their use for pseudo-3D views of vascular blood vessels.
Article
Atomically precise gold nanoclusters are a fascinating class of nanomaterials that exhibit molecule‐like properties and have outstanding photoluminescence (PL). Their ultrasmall size, molecular chemistry, and biocompatibility make them extremely appealing for selective biomolecule labeling in investigations of biological mechanisms at the cellular...
Preprint
Full-text available
The still unmet ability of following the fate of specific cells or molecules within the whole body would give an outstanding breakthrough in the comprehension of disease mechanisms and in the monitoring of therapeutic approaches. Our idea is to push forward the bio-nanotechnology to a level where it serves the most advanced 3D bio-medical imaging t...
Article
The influence of solvent polarity and surface ligand rigidification on the SWIR emission profile of gold nanoclusters with an anistropic surface was investigated. A strong enhancement of the SWIR emis- sion band at 1200 nm was observed when measuring in different local environments: in solution, in polymer composites, and in solids. SWIR in vivo im...
Article
Full-text available
The impact of protein corona on the interactions of nanoparticles (NPs) with cells remains an open question. This question is particularly relevant to NPs which sizes, ranging from tens to hundreds nanometers, are comparable to the sizes of most abundant proteins in plasma. Protein sizes match with typical thickness of various coatings and ligands...
Preprint
Full-text available
Atomically precise gold nanoclusters (Au NCs) are a fascinating class of nanomaterials that exhibit molecule-like properties and have outstanding photoluminescence (PL), which is highly dependent on their structure and chemical environment. Their ultrasmall size, molecular chemistry, and biocompatibility make them extremely appealing for selective...
Article
Nanomedicine has grown structurally complex in order to perform multiple tasks at a time. However, their unsatisfied reliability, uniformity and reproducibility account for the high rates of attrition in translational research. So far, most studies have been one-sidedly focused on the treatment efficacy of inorganic nanoparticles as cancer therapeu...
Cover Page
Full-text available
Deep learning methods provide a fast approach to move noninvasive infrared in vivo imaging to high resolution imaging techniques with full analyses of the vascular network.
Preprint
Full-text available
The impact of protein corona on the interactions of nanoparticles (NPs) with cells remains an open question. This question is particularly relevant to NPs which sizes, ranging from tens to hundreds nanometers, are comparable to the sizes of most abundant proteins in plasma. Protein sizes match with typical thickness of various coatings and ligands...
Article
Full-text available
Shortwave infrared window (SWIR: 1000‐1700 nm) represents a major improvement compared to the NIR‐I region (700‐900 nm) in terms of temporal and spatial resolutions in depths down to 4 mm. SWIR is a fast and cheap alternative to more precise methods such as X‐ray and opto‐acoustic imaging. Main obstacles in SWIR imaging are the noise and scattering...
Conference Paper
We present a method of high resolution, non-invasive, in vivo vascular imaging obtained using watersoluble and bright SWIR-emitting gold nanoclusters presenting an anisotropic surface charge combined with SWIR detection and Monte Carlo processing of the images. We applied this approach to quantify vessel complexity in mice presenting vascular disor...
Preprint
Full-text available
In vivo optical imaging is a fast growing field that offers great perspectives for biomedical applications. In particular, imaging in the shortwave infrared window (SWIR: 1000-1700 nm) represents major improvement compared to the NIR-I region (700-900 nm) in terms of temporal and spatial resolutions in depths down to 4 mm. SWIR is a fast and cheap...
Article
Full-text available
It is commonly accepted that nanoparticles (NPs) can kill bacteria; however, the mechanism of antimicrobial action remains obscure for large NPs that cannot translocate the bacterial cell wall. It is demonstrated that the increase in membrane tension caused by the adsorption of NPs is responsible for mechanical deformation, leading to cell rupture...
Article
Despite advances in the development of bone substitutes and strict aseptic procedures, the majority of failures in bone grafting surgery are related to nosocomial infections. Development of biomaterials combining both osteogenic and antibiotic activity is, therefore, a crucial public health issue. Herein, two types of intrinsically bactericidal tit...
Article
We evaluated the impact of light‐scattering effects on spatial resolution in different SWIR sub‐regions by analyzing two SWIR emissive phantoms made of PDMS‐gold nanoclusters (Au NCs) composite covered with mice skin, or capillary tubes filled with Au NCs or IRDye 800CW at different depth in intralipids and finally, after administration of the Au N...
Article
A simple NIR-II emitting water-soluble system has been developed and applied in vitro and in vivo. In vitro, the fluorophore quickly accumulated in 2D and 3D cell cultures and rapidly reached the tumor in rodents, showing high NIR-II contrast for up to one week. This very efficient probe possesses all the qualities necessary for translation to the...
Article
Full-text available
Ultra-small gold nanoclusters (AuNCs) are increasingly investigated for cancer imaging and radiotherapy enhancement. Fine-tuning the AuNC surface chemistry can optimize augment their pharmacokinetics, its effects on radiotherapy enhancement remain largely...
Article
Full-text available
A library of ultra-small red photoluminescent gold nanoclusters (Au NCs) were synthesized with an increasing amount of positive charges provided by the addition of mono-, di- or trivalent-glutathione modified arginine peptides. We then studied how the arginine content impacted on the interaction of Au NCs with negatively charged artificial lipid bi...
Preprint
Full-text available
We present here a new approach for non-invasive high resolution whole-body vascular imaging in depth by combining water-soluble and bright SWIR-emitting gold nanoclusters revealing an anisotropic surface charge with Monte Carlo image processing of the images. We applied and validated this approach to quantify vessel complexity in transgenic mice pr...
Article
Gold nanoclusters (Au NCs) are an emerging class of luminescent nanomaterials but still suffer from moderate photoluminescence quantum yields. Recent efforts have focused on tailoring their emission properties. Introducing zwitterionic ligands to cap the metallic kernel is an efficient approach to enhance their one-photon excitation fluorescence in...
Article
Full-text available
Photoluminescent gold nanoclusters (Au NCs) were synthesized in one step in aqueous conditions using a mixture of glutathione and (mono or multivalent) glutathione modified arginine peptides. By controlling the ratio of co-ligands, we investigated how the multivalency and the amount of arginines influenced the growth of Au NCs, their surface chemis...
Article
Incorporating anisotropic surface charges on atomically precise gold nanoclusters (Au NCs) led to a strong absorption in the nearinfrared and could generate the formation of self-assembled Au NCs exhibiting an intense absorption band at ~1000 nm. This surface modification showed a striking enhancement of the photoluminescence in the Shortwave Infra...
Article
We report in this study the in vivo biodistribution of ultra-small luminescent gold (Au) particles (∼1.5 nm core size; 17 kDa) so-called nanoclusters (NCs) stabilized by bidentate zwitterionic molecules in subcutaneous (s.c.) and orthotopic glioblastoma mice models. Particular investigations on renal clearance and tumor uptake were performed using...
Conference Paper
Theranostics is an innovative research field that aims to develop high target specificity cancer treatments by administering small metal-based nanoparticles (NPs). This new generation of compounds exhibits diagnostic and therapeutic properties due to the high atomic number of their metal component. In the framework of a combined research program on...
Article
The word "theranostic" derives from the fusion of two terms: therapeutic and diagnostic. It is a promising research field that aims to develop innovative therapies with high target specificity by exploiting the therapeutic and diagnostic properties, in particular for metal-based nanoparticles (NPs) developed to erase cancer. In the framework of a c...
Article
The use of visible/NIR-emitting gold nanoclusters (Au NCs), previously proposed for in vivo imaging, has been limited to some extent by low quantum yields (QYs) and the limited penetration of visible light in tissue. Here we report short wavelength infrared (SWIR, λ = 1–2 μm) emitting Au NCs with a good photoluminescence QY for this wavelength rang...
Chapter
Full-text available
This chapter presents a brief overview of the use of inorganic nanoparticles (NPs) for packaging, food additives, and food analysis to illustrate the benefit of engineered metal-based NPs in food science. It mentions NP migration and toxicity. Metal (Ag, Cu) and metal oxide (ZnO, CuO, TiO2) NPs-based composites are extensively investigated over the...
Article
Gold nanoclusters (Au NCs) are an emerging type of theranostic agents combining therapeutic and imaging features with reduced toxicity. Au NCs stabilized by a zwitterion ligand with a fine control of the metal core size and the ligand coverage were synthesized by wet chemistry. Intense fluorescence signal is reported for the highest ligand coverage...
Chapter
Full-text available
Inorganic materials, nanoparticles (NPs) in particular, have gained a growing interest over the last 20 years for therapy and imaging in the field of cancer, autoimmune, and infectious diseases. The most investigated inorganic NPs applied in nanomedicine could be classified in the list: metal, metal oxide, semiconductors, and lanthanides. This chap...
Article
Nanoparticles combining enhanced cellular drug delivery with efficient fluorescence detection are important tools for the development of theranostic agents. Here we demonstrate this concept by a simple, fast, and robust protocol of cationic polymer-mediated gold nanocluster (Au NCs) self-assembly into nanoparticles (NPs) of ca. 120 nm diameter. An...
Article
Full-text available
This is the first study where graphene is used as a MALDI adjuvant in combination with the traditional matrix α-cyano-4-hydroxycinnamic acid (CHCA) to improve the signal intensity of peptide samples. Use of this amended matrix not only leads to increased signals but also to a higher number of peaks detected in complex samples. Additionally, the use...
Article
12 nm gold nanoparticles induce cell mediated responses accompanied by inflammatory natural killer cell stimulation, whereas 2 nm gold nanoparticles are more efficiently uptaken without inducing dendritic cell maturation or lymphocyte proliferation.
Article
We report the synthesis and characterisation of gold nanoclusters (Au NCs) stabilised by a mixture of zwitterionic and multivalent mannose ligands. Characterisation of this carbohydrated nanosystem confirms its small size (~2 nm), intense red-NIR fluorescence, relatively high affinity to lectin (ConA), and stability in physiological media. Cell stu...
Article
Externally triggered drug release at defined targets allows site- and time-controlled drug treatment regimens. We have developed liposomal drug carriers with encapsulated gold nanoparticles for triggered drug release. Light energy is converted to heat in the gold nanoparticles and released to the lipid bilayers. Localized temperature increase rende...
Article
Synthesis and characterization of gold nanoclusters (Au NCs) stabilized by a zwitterion ligand (Zw) at different Au : Zw ratios are demonstrated. Au NCs exhibit photoluminescence (PL) emission which is tunable from the near infrared (805 nm) to the red spectral window (640 nm) and strongly influenced by the ligand shell size. Optical and chemical i...
Article
Metal (gold, silver, copper, platinum) quantum nano-clusters are an emerging family of fluorescent markers exhibiting unique photophysical properties with tunable electronic structure. This paper will give first an overview on the recent progress to produce stable and highly luminescent metal nanoclusters. In the second part, we will highlight the...
Article
A panel of silver nanoclusters (Ag NCs) protected by glutathione has been produced by collecting them on a plastic surface during an interfacial etching process. Blue-green, yellow and red emitting Ag NCs with size smaller than 2 nm exhibited distinct fluorescence properties (both emission and lifetime). In particular, the yellow emitting Ag NCs we...
Article
We have studied the effect of highly fluorescent gold nanoclusters (Au NCs) (∅< 3nm) stabilized by different ligands on the intracellular accumulation and immune response of human derived-monocyte dendritic cells (DCs). Results indicate that the high uptake efficiency of Au NCs is strongly related to their small size and to the nature of the ligand...
Article
Gold nanoclusters prepared with a controlled amount of Ag exhibit intense fluorescence with a quantum yield of ∼16% and a "quasi-monoexponential" long lifetime of >200 ns. Characterization of the luminescent probes indicates high photostability and easy detection in cells. Additionally, fluorescence enhancement in the presence of proteins was found...
Article
Fluorescent chemical sensors have been widely exploited for the detection and quantification of trace explosives. Their performances are mainly dependent on the sensitive material. Fluorescent organic materials are very efficient in terms of sensitivity, selectivity and response time but their degradation is a major drawback. Sol-gel materials offe...
Article
New types of fluorescent platinum nanoclusters (λmax.= 570 nm) have been synthesized using glutathione for ligand etching. These nanoclusters are mainly in the oxidation state PtI (90%) exhibiting an intense fluorescence signal (QY17%) in the yellow region and lead to the formation of blue-emitting species for a long etching time process.
Article
Multifunctional nanoparticles (NPs) combining the superparamagnetism of Mn-Zn ferrite and the fluorescence property of gold nanoclusters (NCs) have been prepared by wet chemistry. Magnetic NPs synthesized by co-precipitation method were coated several times with oppositely charged polyelectrolytes (PEs) using the layer-by-layer technique. Common te...
Article
Human transferrin has been biolabelled with gold nanoclusters (Au NCs) using a simple, fast and non-toxic method. These nanocrystals (<2 nm) are stabilized in the protein via sulfur groups and have a high fluorescence emission in the near infrared region (QY=4.3%; λem=695 nm). Structural investigation and photophysical measurements show a high popu...
Article
Recently, multifunctional silica nanoparticles have been investigated extensively for their potential use in biomedical applications. We have prepared sub-micron monodisperse and stable multifunctional mesoporous silica particles with a high level of magnetization and fluorescence in the near infrared region using an one-pot synthesis technique. Co...
Article
In this paper we describe the synthesis and the optimisation of a new family of fluorescent core–shell nanoparticle using protein-stabilised gold nanoclusters. Fluorescent gold nanoclusters (<2 nm) entrapped in bovine serum albumin (BSA) protein were loaded in a 100 nm-silicananoparticle with an optimal concentration of 3% (w/w). These nanoparticle...
Article
When designing devices for biomedical diagnostics, increasing the signal to noise ratio is often critical for achieving clinically relevant sensitivity and limits of detection (LOD). In antibody-based assays, the measured signal can be amplified through the replacement of molecular fluorophores with doped nanoparticles (NP). However, the benefits o...
Article
In this work, we used a model assay system (polyclonal human IgG–goat antihuman IgG) to elucidate some of the key factors that influence the analytical performance of bioassays that employ metal-enhanced fluorescence (MEF) using silver nanoparticles (NPs). Cy5 dye was used as the fluorescent label, and results were compared with a standard assay pe...
Article
Silver nanoplates (NPTs) were prepared by a seed-mediated growth method with different diameters (d = 25, 32, 53, and 100 nm) and with thicknesses of approximately 10 nm in all cases. As the concentration of silver seeds increased, the diameter of the nanoplates increased, resulting in an overall shift in the localized surface plasmon resonance (LS...
Article
In this presentation we describe strategies that will yield substantial enhancements in the analytical performance of fluorescence-based biochip platforms, especially for biomedical diagnostic applications. In particular, the focus is on optimisation of the signal-to-noise ratio (SNR) with a view to lowering the limit of detection (LOD). These stra...
Article
There is substantial interest in the development of near-infrared dye-doped nanoparticles (NPs) for a range of applications including immunocytochemistry, immunosorbent assays, flow cytometry, and DNA/protein microarray analysis. The main motivation for this work is the significant increase in NP fluorescence that may be obtained compared with a si...
Article
Sol–gel waveguides have been realized using a mixture of zirconium and titanium alkoxides with 3-Glycidoxypropyltrimethoxysilane (Glymo) as organic modifier. The molar ratio metal (Ti,Zr)/Glymo was 70/30 in order to obtain a material with high refractive index. Coumarin30 dye was added into the matrix during the synthesis with a concentration 2×10−...
Article
Full-text available
Sol–gel derived inorganic–organic hybrid materials (HYBRIMERs) have shown a great potential for planar and channel waveguides due to their high photosensitivity, low-cost processing and good suitability for doping. These materials have been synthesized with a high content of titanium (40%) and with three different chelating agents: acetylacetone, m...

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Projects

Projects (3)
Project
A single nanomedicine agent based on gold nanoclusters is proposed to improve optical image-guidance for surgery and intra-operative phototherapy, and in a second post-operative step, for radiotherapy.
Project
In this project, we will set up a SWIR imaging platform to demonstrate the benefit of monitoring blood and lymphatic vasculatures non invasively in the whole body of pathological animal models. Through the analyse of temporal 2D and 3D image reconstructions results should bring insights on the mechanisms of neoangiogenesis, cancer vascular and lymphatic abnormalities and their influence on mammary cancer progression and metastasis.
Project
Understanding the mechanisms of translocation, elucidating the role of nano-objects translocation through biological membranes, barriers, lipid vesicles and artificial bilayers.