Nanoparticle size influences the proliferative responses of lymphocyte subpopulations

International audience12 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

Conventional Matrices Loaded Onto a Graphene Layer Enhances MALDI-TOF/TOF Signal: Its Application to Improve Detection of Phosphorylated Peptides

International audienceThis 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 of graphene has a stabilizing effect that can also be exploited to improve the detection of easily cleavable molecules

Zwitterion functionalized gold nanoclusters for multimodal near infrared fluorescence and photoacoustic imaging

International audienceGold 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 whereas photoacoustic signal is stronger for the largest metal core. The best Au NCs candidate with an average molecular weight of 17 kDa could be detected with high sensitivity on a 2D-NIR imaging instrument (LOD = 2.3 µM) and by photoacoustic imaging. In vitro and in vivo experiments demonstrate an efficient cell uptake in U87 cell lines, a fast renal clearance (t 1/2 α = 6.5±1.3 min) and a good correlation between near 2 infrared fluorescence and photoacoustic measurements to follow the early uptake of Au NCs in liver

La couronne de protéines module l'interaction des nanoparticules en pointe avec les bicouches lipidiques

International audienceThe 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 layers, usually present at the surfaces of larger NPs. Such size match may affect the properties and the designed function of NPs. We offer a direct demonstration of how protein corona can dramatically change the interaction mode between NPs and 1 lipid bilayers. To this end, we choose the most extreme case of NP surface modification: nanostructures in the form of rigid spikes of 10-20 nm length at the surface of gold nanoparticles. In the absence of proteins we observe the formation of reversible pores when spiky NPs absorb on lipid bilayers. In contrast, the presence of bovine serum albumin (BSA) proteins adsorbed at the surface of spiked NPs, effectively reduce the length of spikes exposed to the interaction with lipid bilayers. Thus, protein corona changes qualitatively the dynamics of pore formation, which is completely suppressed at high protein concentrations. These results suggest that protein corona can not only be critical for interaction of NPs with membranes, it may change their mode of interaction, thus offsetting the role of surface chemistry and ligands

Synthesis and characterization of human transferrin-stabilized gold nanoclusters.

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 population of clusters formed of 22-33 gold atoms covalently bound to the transferrin. In solutions with pH ranging from 5 to 10 and in buffer solutions (PBS, HEPES), those biolabelled proteins exhibit a good stability. No significant quenching effect of the fluorescent transferrin has been detected after iron loading of iron-free transferrin (apoTf) and in the presence of a specific polyclonal antibody. Additionally, antibody-induced agglomeration demonstrates no alteration in the protein activity and the receptor target ability. MTT and Vialight® Plus tests show no cytotoxicity of these labelled proteins in cells (1 µg ml(-1)-1 mg ml(-1)). Cell line experiments (A549) indicate also an uptake of the iron loaded fluorescent proteins inside cells. These remarkable data highlight the potential of a new type of non-toxic fluorescent transferrin for imaging and targeting

anoclusters métalliques pour les applications biomédicales : Vers des études in vivo

International audienceIn 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 therapeutic activities under irradiation. Furthermore, due to their size smaller than 6 nm and unique biophysical properties, they also present intriguing behaviors in biological and physio-pathological environments. In this review, we aim to present the last researches published on such nanoparticles in animals. We also propose guidelines to identify the main physico-chemical parameters that govern Au NCs behavior after administration in small animals, notably concerning their renal elimination and their ability to accumulate in tumors. Then, we present recent advances for their use as theranostic agents putting them in parallel with others contrast agents

Gold nanoclusters for biomedical applications:toward in vivo studies

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Protein-coated nanoparticles exhibit Lévy flights on a suspended lipid bilayer

International audienceLateral diffusion of nano-objects on lipid membranes is a crucial process in cell biology. Recent studies indicate that nanoparticle lateral diffusion is affected by the presence of membrane proteins and deviates from Brownian motion. Gold nanoparticles (Au NPs) stabilized by short thiol ligands were dispersed near a free-standing bilayer formed in a 3D microfluidic chip. Using dark-field microscopy, the position of single NPs at the bilayer surface was tracked over time. Numerical analysis of the NP trajectories shows that NP diffusion on the bilayer surface corresponds to Brownian motion. The addition of bovine serum albumin (BSA) protein to the solution led to the formation of a protein corona on the NP surface. We found that protein-coated NPs show anomalous superdiffusion and that the distribution of their relative displacement obeys Lévy flight statistics. This superdiffusive motion is attributed to a drastic reduction in adhesive energies between the NPs and the bilayer in the presence of the protein corona. This hypothesis was confirmed by numerical simulations mimicking the random walk of a single particle near a weakly adhesive surface. These results may be generalized to other classes of nano-objects that experience adsorption-desorption behaviour with a weakly adhesive surface

Engineering Liganded Gold Nanoclusters as Efficient Theranostic Agents for Cancer Applications

International audienceLuminescent gold nanoclusters are rapidly gaining attention as efficient theranostic targets for imaging and therapeutics. Indeed, their ease of synthesis, their tunable optical properties and tumor targeting make them potential candidates for sensitive diagnosis and efficacious therapeutic applications. This concept highlights the key components for designing gold nanoclusters as efficient theranostics focusing on application in the field of oncology