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Platinum-based drugs are popular in clinics as chemotherapeutic agents to treat solid tumors. However, severe side effects such as nephro- and neurotoxicity impose strict dosage limitations that can lead to the development of drug resistance and tumor relapse. To overcome these issues Pt(IV) prodrugs and platinum delivery systems might represent the next generation of platinum-based drugs. In this study four novel Pt(II) complexes (namely, PEG-Glu-Pt-EDA, PEG-Glu-Pt-DACH, PEG-Mal-Pt-EDA and PEG-Mal-Pt-DACH) were synthesized and a general strategy to covalently bind them to iron oxide nanoparticles was developed. The intracellular uptake and cell distribution studies of Pt-tethered magnetic nanoparticles on breast and ovarian cancer cell line models indicate that binding of the Pt complexes to the nanoparticles facilitates, for all the complexes, cellular internalization. Moreover, the magnetic nanoparticles (MNPs), as shown in a magnetofection experiment, enhance the uptake of MNP-Pt conjugates if a magnet is placed beneath the culture dish of tumor cells. As shown by a Pt release experiment, intranuclear platinum quantification and TEM analysis on cell sections, the presence of a pH-sensitive dicarboxylic group coordinating the Pt complex, triggers platinum dissociation from the NP surface. In addition, the triazole moiety facilitates endosomal swelling and the leakage of platinum from the endosomes with intranuclear localization of platinum release by the NPs. Finally, as assessed by MTT, caspase, calcein/ethidium bromide live/dead assays, among the four NP-Pt conjugates, the NP-Glu-Pt-EDA complex having a glutamate ring and ethylenediamine as a chelating amine group of the platinum showed higher cytotoxicity than the other three MNP–platinum conjugates This work was funded by the European Research Council (starting grant ICARO, Contract No. 678109) and partially supported by the European project Magnifyco (Contract No. NMP4-SL-2009-228622) and by the Project FISR—C.N.R. “Tecnopolo di Nanotecnologia e Fotonica per la Medicina di Precisione”— (CUPB83B17000010001). This work was also supported by the Spanish Agencia Estatal de Investigación (AEI) and the ERDF (CTQ2016-78423-R), and by the Xunta de Galicia and the ERDF (EM2014/011) and Centro singular de investigación de Galicia accreditation 2016–2019, (ED431G/09) SI

For their remarkable biomimetic properties implying strong modulation of the intracellular and extracellular redox state, cerium oxide nanoparticles (also termed "nanoceria") were hypothesized to exert a protective role against oxidative stress associated with the harsh environmental conditions of spaceflight, characterized by microgravity and highly energetic radiations. Nanoparticles were supplied to proliferating C2C12 mouse skeletal muscle cells under different gravity and radiation levels. Biological responses were thus investigated at a transcriptional level by RNA next-generation sequencing. Lists of differentially expressed genes (DEGs) were generated and intersected by taking into consideration relevant comparisons, which led to the observation of prevailing effects of the space environment over those induced by nanoceria. In space, upregulation of transcription was slightly preponderant over downregulation, implying involvement of intracellular compartments, with the majority of DEGs consistently over- or under-expressed whenever present. Cosmic radiations regulated a higher number of DEGs than microgravity and seemed to promote increased cellular catabolism. By taking into consideration space physical stressors alone, microgravity and cosmic radiations appeared to have opposite effects at transcriptional levels despite partial sharing of molecular pathways. Interestingly, gene ontology denoted some enrichment in terms related to vision, when only effects of radiations were assessed. The transcriptional regulation of mitochondrial uncoupling protein 2 in space-relevant samples suggests perturbation of the intracellular redox homeostasis, and leaves open opportunities for antioxidant treatment for oxidative stress reduction in harsh environments.

The interplay between nanoparticles (NPs) and cell membranes is extremely important with regard to using NPs in biology applications. With the aim of unraveling the dominating factors on the molecular scale, we have studied the interaction between polymer-coated semiconductor nanorods (NRs) made of cadmium selenium/cadmium sulfur and model lipid membranes. The zeta potential (ζ) of the NRs was tuned from having a negative value (-24 mV) to having a positive one (+11 mV) by changing the amine content in the polymer coating. Supported lipid bilayers (SLBs) and lipid monolayers (LMs) were used as model membranes. Lipid mixtures containing anionic or cationic lipids were employed in order to change the membrane ζ from -77 to +49 mV; lipids with saturated hydrophobic chains were used to create phase-separated gel domains. NR adsorption to the SLBs was monitored by quartz crystal microbalance with dissipation monitoring; interactions with LMs with the same lipid composition were measured by surface pressure-area isotherms. The results showed that the NRs only interact with the model membrane if the mutual Δζ is higher than 70 mV; at the air-water interface, positively charged NRs remove lipids from the anionic lipid mixtures, and the negative ones penetrate the space between the polar heads in the cationic mixtures. However, the presence of gel domains in the membrane inhibits this interaction. The results of the Derjaguin-Landau-Verwey-Overbeek model frame indicate that the interaction occurs not only due to electrostatic and van der Waals forces, but also due to steric and/or hydration forces.

In the field of nanomedicine, superparamagnetic nanoparticles are one of the most studied nanomaterials for theranostics. In this study, a one-pot synthesis of magnetic nanoparticles is presented, with an increased control on particle size from 10 to 40 nm. Monitoring of vacuum level is introduced here as a crucial parameter for achieving a fine particle morphology. The magnetic properties of these nanoparticles are highly affected by disorders or mismatches in crystal structure. A prolonged oxidation step is applied to the obtained nanoparticles to transform the magnetic phases into a pure maghemite one, confirmed by high-resolution X-ray photoelectron spectroscopy analysis, by Mössbauer spectrometry and, indirectly, by increased performances in magnetization curves and in relaxation times. Afterward, the attained nanoparticles are transferred into water by a nonderivatized dextran coating. Thermogravimetric analysis confirms that polysaccharide molecules replace oleic acid on the surface by stabilizing the particles in the aqueous phase and culture media. Preliminary in vitro test reveals that the dextran-coated nanoparticles are not passively internalized from the cells. As a proof of concept, a secondary layer of chitosan assures a positive charge to the nanoparticle surface, thus enhancing cellular internalization.

Lithium-sulfur batteries are the most promising candidates for next-generation energy storage devices owing to their high theoretical specific capacity of 1675 mAh g-1 and high theoretical energy density of approximately 3500 Wh kg-1 . However, the lack of cathode active materials with appropriate electrical conductivities and stability coupled with an inexpensive and industrially compatible production process has so far hindered the development of practical devices. Here, a facile preparation pathway is reported for the production of a sulfur-carbon composite active material by drying a mixture of highly conductive few-layer graphene (FLG) flakes (produced by exploiting an innovative wet jet milling process with a yield of ≈100 % and production capability of ≈23.5 g h-1 ) with elemental sulfur, using ethanol as an environmentally friendly solvent. The designed sulfur-FLG composite shows excellent electrochemical results. The assembled lithium-sulfur battery exhibits a stable rate capability up to a current rate of 2C, a coulombic efficiency approaching 100 % for 300 cycles at the current rate of C/4 (420 mA g-1 ), and a long cycle life up to 500 cycles delivering around 600 mAh g-1 at 2C (3350 mA g-1 ).

The realization of a high-performance Li-ion full-cell with an anode prominently based on silicon, which can surpass the energy densities of commercial graphite-based Li-ion batteries and cyclability compatible for industrial applications, is still a challenge. Here, we report a Li-ion full-cell that combines a silicon/graphene/carbon (Si/G/C) nanocomposite anodic material, with a commercial LiNi0.33Mn0.33Co0.33O2 (NMC111) cathode. Using a pre-lithiation technique, the proposed Li-ion full-cell exhibits an energy density of ∼400 Wh kg−1 at the electrode material level, with a capacity >1.6 mAh cm−2 and a capacity retention exceeding 90% after 300 cycles at C/2. These performances have been achieved by properly designing the anode material composed by Si nanoparticles wrapped by few-layer graphene flakes. An additional carbon coating is used to further improve the electron conductivity and mechanical integrity of the anodic structure upon charge/discharge cycles. The remarkable performance of the full-cell considering the scalability of the Si-based anode synthesis is a step forward towards the commercialization of high-capacity and high-energy density Li-ion batteries.

A NiO@C composite anode is prepared through an alternative synthesis route involving precipitation of a carbon precursor on NiO nanopowder, annealing under argon to form a Ni core, and oxidation at moderate temperature to get metal oxide particles whilst retaining carbon and metallic Ni in traces. The electrode reversibly reacts in lithium cells by the typical conversion process occurring in a wide potential range with the main electrochemical activity at 1.3 V vs. Li+/Li during discharge and at 2.2 V vs. Li+/Li during charge. The NiO@C material exhibits highly improved behavior in a lithium half-cell compared to bare NiO due to faster electrode kinetics and superior stability over electrochemical displacement, leading to a reversible capacity approaching 800 mAh g−1, much enhanced cycle life and promising rate capability. The applicability of the NiO@C anode is further investigated in a lithium-ion NiO@C/LiNi⅓Co⅓Mn⅓O2 cell, which operates at about 2.5 V delivering about 160 mAh g−1 with respect to the cathode mass. The cell exhibits stable response upon 80 cycles at a C/2 rate with coulombic efficiency ranging from 97% to 99%.

We report a facile synthesis of cube-shaped CoxFe3–xO4 nanocrystals (NCs), which could be finely tuned in terms of NC size (from 15 to 27 nm) and cobalt stoichiometry (from 0.1 to 0.7). These particles exhibited high specific absorption rate (SAR) values, relevant for magnetic hyperthermia, and high relaxivity values, significant for magnetic resonance imaging applications. The peculiarity of these NCs is that already at low frequencies (such as 105 kHz, a working frequency used on human patients), they display SAR values that are three-times as large as those of iron oxide nanocubes of comparable sizes (and which were already considered outstanding). The highest SAR value recorded on the NCs reported here (915 ± 10 W/g(Co+Fe) at 105 kHz and 32 kAm–1) refers to particles with cubic shape, 20 ± 2 nm edge size, and Co stoichiometry between 0.6 and 0.7. The highest r2 value (958 mM–1 s–1) was instead recorded on nanocubes with Co stoichiometry around 0.5/0.6 and size of 20 ± 2 nm. Remarkably, only at this sp...

We report on the preparation of polycarbonate-based graphene (PC/G) composites, by using a simple and scalable solution blending method to disperse single (SLG) and few layer (FLG) graphene flakes, prepared by liquid phase exfoliation (LPE), in the polymer matrix. A solvent-exchange process is carried out to re-disperse the exfoliated SLG/FLG flakes in an environmentally friendly solvent, i.e. 1,3dioxolane, which is also used to dissolve the polycarbonate pellets, thus facilitating the mixing of the polymer dispersion with the SLG/FLG flakes. The loading of SLG/FLG flakes improves the mechanical and thermal properties, as well as the electrical conductivity of the polymer, reaching a +26% improvement of the elastic modulus at 1 wt% loading, and an electrical conductivity 10^-3 S m^-1 at 10 wt% with a percolation threshold achieved at 0.55 vol%. The as-prepared PC/G composite with the aforementioned reinforced properties can be a promising material for 3D printing-based applications.

In dieser Zuschrift wird uber eine universelle Methode zur Herstellung von selbsttragenden Aerogelen aus kolloidalen Nanopartikeln (NP) berichtet. Dafur werden die NP eingefroren und anschliesend gefriergetrocknet. Das bedeutet, dass die kolloidalen NP ohne vorherige Gelierung (wie bisher bei herkommlichen Aero- und Kryogel-Verfahren ublich) direkt in trockene, aerogelahnliche monolithische Uberstrukturen uberfuhrt werden konnen. Die Anordnung der NP zu einer Uberstruktur ist ein rein physikalischer Prozess und dadurch vielfaltig einsetzbar, was bedeutet, dass die Kryogelierung auf Edelmetall-, Metalloxid- und Halbleiter-NP angewendet werden kann. Die Kryogelierung beeinflusst die Oberflachenchemie oder die NP-Form in der entstehenden Morphologie dabei nicht. Unter idealen Bedingungen sind auch die Volumina und die Formen von gefrorenem NP-Kolloid und Aerogel gleich gros. Dies ermoglicht es, mit der Methode dunne, gleichmasige Aerogelfilme und andere Geometrien von Aerogelmonolithen herzustellen. Abschliesend werden die physikochemischen Eigenschaften der Aerogele diskutiert.

Magnetic nanobeads are synthesized by coprecipitation of hollow iron oxide nanoparticles and an amphiphilic polymer. The resulting nanobeads can be tuned in diameter and nanoparticle content. X-ray absorption near-edge structure (XANES) spectroscopy and superconducting quantum interferometer device (SQUID) characterization of the nanobeads reveal that they exhibit an increased effective magnetic anisotropy as compared to the individual nanoparticles, despite that no structural changes of the particles had occurred during the embedding process into the polymer. The spin-spin relaxation times of the pristine hollow nanoparticles and of the final magnetic nanobeads reveal a high R2 relaxivity of 206 s-1 mM-1 for the magnetic nanobeads. This result should enable their application as negative contrast enhancing agents in magnetic resonance imaging., We are grateful for financial support from the European project Magnifyco (contract NMP4-SL-2009-228622), by the Italian AIRC project (contract no. 14527 to T.P.), EU-ITN network Mag(net)icFun (PITN-GA-2012-290248), and by the Italian FIRB project (Nanostructured oxides, contract no. 588 BAP115AYN). N.C.B. is grateful for financial support from the German Federal Ministry of Education and Research (BMBF) within the framework of the program NanoMatFutur (support code 03X5525). Funding from Spanish MINECO through grants MAT2011-27470-C02-02 and CSD2009_00013 is greatly acknowledged.

With the aim of producing Au–FexOy dimers with outstanding heating performances under magnetic hyperthermia conditions applicable to human patients, here we report two synthesis routes, a two-pot and a one-pot method. The addition of chloride ions and the absence of 1,2-hexadecanediol (HDDOL), a commonly used chemical in this synthesis, are the key factors that enable us to produce dimers at low temperature with crystalline iron oxide domains in the size range between 18–39 nm that is ideal for magnetic hyperthermia. In the case of two-pot synthesis, in which no chloride ions are initially present in the reaction pot, dimers are obtained only at 300 1C. In order to lower the reaction temperature to 200 1C and to tune the size of the iron oxide domain, the addition of chloride ions becomes the crucial parameter. In the one-pot method, the presence of chloride ions from the start of the synthesis (as counter ions of the gold salt precursor) enables a prompt formation of dimers directly at 200 1C. In this case, the reaction time is the main parameter used to tune the iron oxide size. A record value of specific absorption rates (SARs) up to 1300 W gFe1 at 330 kHz and 24 kA m1 was measured for dimers with an iron oxide domain of 24 nm in size.

A versatile method to fabricate self-supported aerogels of nanoparticle (NP) building blocks is presented. This approach is based on freezing colloidal NPs and subsequent freeze drying. This means that the colloidal NPs are directly transferred into dry aerogel-like monolithic superstructures without previous lyogelation as would be the case for conventional aerogel and cryogel fabrication methods. The assembly process, based on a physical concept, is highly versatile: cryogelation is applicable for noble metal, metal oxide, and semiconductor NPs, and no impact of the surface chemistry or NP shape on the resulting morphology is observed. Under optimized conditions the shape and volume of the liquid equal those of the resulting aerogels. Also, we show that thin and homogeneous films of the material can be obtained. Furthermore, the physical properties of the aerogels are discussed.

Recently, plasmonic copper sulfide (Cu2–xS) nanocrystals (NCs) have attracted much attention as materials for photothermal therapy (PTT). Previous reports have correlated photoinduced cell death to the photothermal heat mechanism of these NCs, and no evidence of their photodynamic properties has been reported yet. Herein we have prepared physiologically stable near-infrared (NIR) plasmonic copper sulfide NCs and analyzed their photothermal and photodynamic properties, including therapeutic potential in cultured melanoma cells and a murine melanoma model. Interestingly, we observe that, besides a high PTT efficacy, these copper sulfide NCs additionally possess intrinsic NIR induced photodynamic activity, whereupon they generate high levels of reactive oxygen species. Furthermore, in vitro and in vivo acute toxic responses of copper sulfide NCs were also elicited. This study highlights a mechanism of NIR light induced cancer therapy, which could pave the way toward more effective nanotherapeutics.

International audience; Safe implementation of nanotechnology and nanomedicine requires an in-depth understanding of the life cycle of nanoparticles in the body. Here, we investigate the long-term fate of gold/iron oxide heterostructures after intravenous injection in mice. We show these heterostructures degrade in vivo and that the magnetic and optical properties change during the degradation process. These particles eventually eliminate from the body. The comparison of two different coating shells for heterostructures, amphiphilic polymer or polyethylene glycol, reveals the long lasting impact of initial surface properties on the nanocrystal degradability and on the kinetics of elimination of magnetic iron and gold from liver and spleen. Modulation of nanoparticles reactivity to the biological environment by the choice of materials and surface functionalization may provide new directions in the design of multifunctional nanomedicines with predictable fate.

We report a highly reproducible route to synthesize iron oxide nanoparticles (IONPs) with control over size and shape and with size dispersions around 10%. By tuning the relative ratio of squalane to dibenzyl ether, which were used as solvents in the synthesis, the size of the particles could be varied from 14 to around 100 nm, while their shape evolved from cubic (for size ranges up to 35 nm) to truncated octahedra and octahedra (for sizes from 40 nm up to 100 nm). Fine tuning of the size within each of these ranges could be achieved by varying the heating ramp and the iron precursor to decanoic acid ratio. We also demonstrate direct water transfer of the as-synthesized IONPs via in situ ligand exchange with gallol polyethylene glycol molecules, the latter simply added to the crude nanocrystal mixture at 70 degrees C. The specific absorption rate (SAR) values measured on the water transferred IONPs, at frequencies and applied magnetic fields that are considered safe for patients, confirmed their high heating performance. Finally, this method allows the transfer of 35 nm nanocubes as individually coated and stable particles to the water phase. For the first time, the heating performance of such large IONPs has been studied. This work uncovers the possibility of using large IONPs for magnetic hyperthermia in tumor therapy.

International audience; There is a great deal of interest in the development of nanoplatforms gathering versatility and multifunctionality. The strategy reported herein meets these requirements and further integrates a cell-friendly shell in a bio-inspired approach. By taking advantage of a cell mechanism of biomolecule transport using vesicles, we engineered a hybrid biogenic nanoplatform able to encapsulate a set of nanoparticles regardless of their chemistry or shape. As a proof of versatility, different types of hybrid nanovesicles were produced: magnetic, magnetic-metallic and magnetic-fluorescent vesicles, either a single component or multiple components, combining the advantageous properties of each integrant nanoparticle. These nanoparticle-loaded vesicles can be manipulated, monitored by MRI and/or fluorescence imaging methods, while acting as efficient nano-heaters. The resulting assets for targeting, imaging and therapy converge for the outline of a new generation of nanosystems merging versatility and multifunctionality into a bio-camouflaged and bio-inspired approach.