Magnetically Induced Thermal Effects on Tobacco Mosaic Virus-Based Nanocomposites for a Programmed Disassembly of Protein Cages.

Protein cages are promising tools for the controlled delivery of therapeutics and imaging agents when endowed with programmable disassembly strategies. Here, we produced hybrid nanocomposites made of tobacco mosaic virus (TMV) and magnetic iron oxide nanoparticles (IONPs), designed to disrupt the viral protein cages using magnetically induced release of heat. We studied the effects of this magnetic hyperthermia on the programmable viral protein capsid disassembly using (1) elongated nanocomposites of TMV coated heterogeneously with magnetic iron oxide nanoparticles (TMV@IONPs) and (2) spherical nanocomposites of polystyrene (PS) on which we deposited presynthesized IONPs and TMV via layer-by-layer self-assembly (PS@IONPs/TMV). Notably, we found that the extent of the disassembly of the protein cages is contingent upon the specific absorption rate (SAR) of the magnetic nanoparticles, that is, the heating efficiency, and the relative position of the protein cage within the nanocomposite concerning the heating sources. This implies that the spatial arrangement of components within the hybrid nanostructure has a significant impact on the disassembly process. Understanding and optimizing this relationship will contribute to the critical spatiotemporal control for targeted drug and gene delivery using protein cages.

Programming an Enhanced Uptake and the Intracellular Fate of Magnetic Microbeads.

This study compares two kinds of magnetic microbeads with different surface features and cell entry pathways, aiming to provide insights into how to program their cell uptake and intracellular fate. It is found that a rougher surface enhances the cell uptake of the microbeads, regardless of whether they are pulled by a magnetic field gradient or adsorbed by the cell membrane. However, the entry route affects the intracellular localization of the microbeads: The magnetically dragged microbeads reach the cytoplasm, while the adsorbed microbeads stay in the late endosomes and lysosomes. This suggests that different strategies can be used to target different cellular compartments with magnetic microbeads. Moreover, it is demonstrated that the cells containing the microbeads can be moved and regrown at specific locations by applying a magnetic field gradient, showing the potential of these magnetic microbeads for cell delivery and manipulation.

Interfaceless Exchange Bias in CoFe2O4 Nanocrystals.

Oxidized cobalt ferrite nanocrystals with a modified distribution of the magnetic cations in their spinel structure give place to an unusual exchange-coupled system with a double reversal of the magnetization, exchange bias, and increased coercivity, but without the presence of a clear physical interface that delimits two well-differentiated magnetic phases. More specifically, the partial oxidation of cobalt cations and the formation of Fe vacancies at the surface region entail the formation of a cobalt-rich mixed ferrite spinel, which is strongly pinned by the ferrimagnetic background from the cobalt ferrite lattice. This particular configuration of exchange-biased magnetic behavior, involving two different magnetic phases but without the occurrence of a crystallographically coherent interface, revolutionizes the established concept of exchange bias phenomenology.

Magnetically propelled chained nanocomposites for biologically relevant media exploration.

Elongated nanostructures to be remotely and magnetically propelled in biologically relevant media, have gained attention as offering themselves as effective tools or carriers in theragnostics applications. However, the magnetic actuation associated remains challenging due to the lack of mechanical information in the media of interest, taking into account biophysical or biomedical purposes. In this study, we detail the magnetic actuation of magnetically propelled chained nanocomposites considering their dynamics, in which their velocity can be modulated in terms of the viscosity of the medium considered, given a magnetic field gradient. Simpler cases of distilled water, a water/glycerol mixture and a fluid made of cell extracts (imitating the cytosol of cells) of known viscosity are the basis experiments for the study of more complex media inside HeLa cells, murine NIH-3T3 fibroblasts and zebrafish larvae, offering the mechanical information required. The experimental results indicate that the magnetically propelled performance of the chained nanostructures can be precisely controlled in potentially changing scenarios, where drug and heat delivery, magnetic separation, or microfluidic technologies are demanded, using a magnetic field gradient and providing good estimations of the dynamical parameters involved.

Oxidative Precipitation Synthesis of Calcium-Doped Manganese Ferrite Nanoparticles for Magnetic Hyperthermia.

Superparamagnetic nanoparticles are of high interest for therapeutic applications. In this work, nanoparticles of calcium-doped manganese ferrites (CaxMn1-xFe2O4) functionalized with citrate were synthesized through thermally assisted oxidative precipitation in aqueous media. The method provided well dispersed aqueous suspensions of nanoparticles through a one-pot synthesis, in which the temperature and Ca/Mn ratio were found to influence the particles microstructure and morphology. Consequently, changes were obtained in the optical and magnetic properties that were studied through UV-Vis absorption and SQUID, respectively. XRD and Raman spectroscopy studies were carried out to assess the microstructural changes associated with stoichiometry of the particles, and the stability in physiological pH was studied through DLS. The nanoparticles displayed high values of magnetization and heating efficiency for several alternating magnetic field conditions, compatible with biological applications. Hereby, the employed method provides a promising strategy for the development of particles with adequate properties for magnetic hyperthermia applications, such as drug delivery and cancer therapy.

Synergistic Interaction of Clusters of Iron Oxide Nanoparticles and Reduced Graphene Oxide for High Supercapacitor Performance.

Supercapacitors have been recognized as one of the more promising energy storage devices, with great potential use in portable electronics and hybrid vehicles. In this study, a composite made of clusters of iron oxide (Fe3O4-γFe2O3) nanoparticles and reduced graphene oxide (rGO) has been developed through a simple one-step solvothermal synthesis method for a high-performance supercapacitor electrode. Electrochemical assessment via cyclic voltammetry, galvanostatic charge-discharge experiments, and electrochemical impedance spectroscopy (EIS) revealed that the Fe3O4-γFe2O3/rGO nanocomposite showed much higher specific capacitance than either rGO or bare clusters of Fe3O4-γFe2O3 nanoparticles. In particular, specific capacitance values of 100 F g-1, 250 F g-1, and 528 F g-1 were obtained for the clusters of iron oxide nanoparticles, rGO, and the hybrid nanostructure, respectively. The enhancement of the electrochemical performance of the composite material may be attributed to the synergistic interaction between the layers of graphene oxide and the clusters of iron oxide nanoparticles. The intimate contact between the two phases eliminates the interface, thus enabling facile electron transport, which is key to attaining high specific capacitance and, consequently, enhanced charge-discharge time. Performance evaluation in consecutive cycles has demonstrated that the composite material retains 110% of its initial capacitance after 3000 cycles, making it a promising candidate for supercapacitors.

Tuning the drug multimodal release through a co-assembly strategy based on magnetic gels.

Self-assembled short peptide-based gels are highly promising drug delivery systems. However, implementing a stimulus often requires screening different structures to obtain gels with suitable properties, and drugs might not be well encapsulated and/or cause undesirable effects on the gel's properties. To overcome this challenge, a new design approach is presented to modulate the release of doxorubicin as a model chemotherapeutic drug through the interplay of (di)phenylalanine-coated magnetic nanoparticles, PEGylated liposomes and doxorubicin co-assembly in dehydropeptide-based gels. The composites enable an enhancement of the gelation kinetics in a concentration-dependent manner, mainly through the use of PEGylated liposomes. The effect of the co-assembly of phenylalanine-coated nanoparticles with the hydrogel displays a concentration and size dependence. Finally, the integration of liposomes as doxorubicin storage units and of nanoparticles as composites that co-assemble with the gel matrix enables the tuneability of both passive and active doxorubicin release through a thermal, and a low-frequency alternating magnetic field-based trigger. In addition to the modulation of the gel properties, the functionalization with (di)phenylalanine improves the cytocompatibility of the nanoparticles. Hereby, this work paves a way for the development of peptide-based supramolecular systems for on-demand and controlled release of drugs.

Manganese Ferrite Nanoparticles Encapsulated into Vitamin E/Sphingomyelin Nanoemulsions as Contrast Agents for High-Sensitive Magnetic Resonance Imaging.

Magnetic resonance imaging (MRI) is one of the most powerful non-invasive imaging modalities used in clinics due to its great spatial resolution and excellent soft-tissue contrast, though still less sensitive than other techniques such as the nuclear imaging modalities. This lack of sensitivity can be improved with the use of contrast agents based on nanomaterials. In recent years, researchers have focused on the development of magnetic nanoparticles, given their role as enhancers of the contrast signal based on the magnetic resonance. Manganese ferrite nanoparticles stand out, given their high magnetic susceptibility and magnetic soft nature. Herein, 10 nm MnFe2 O4 nanoparticles, functionalized with the natural antioxidant vitamin E (VitE-MFO) are encapsulated into simple, biodegradable and non-toxic nanoemulsions (NEs), by a reproducible one-step method obtaining stable 150 nm-sized magnetic nanoemulsions (VitE-MFO-NEs). After encapsulation, the superparamagnetic properties of VitE-MFO are maintained and MR imaging studies reveal an extremely high transverse relaxivity for VitE-MFO-NEs (652.9 × 10-3  m-1  s-1 ), twofold higher than VitE-MFO value. Moreover, VitE-MFO-NEs show great in vivo biocompatibility and good signal in in vivo and ex vivo MRI, which indicates their great potential for biomedical imaging enhancing the negative MR contrast and significantly improving the sensitivity of MRI.

Impact of Citrate and Lipid-Functionalized Magnetic Nanoparticles in Dehydropeptide Supramolecular Magnetogels: Properties, Design and Drug Release.

Currently, the nanoparticle functionalization effect on supramolecular peptide-based hydrogels remains undescribed, but is expected to affect the hydrogels' self-assembly and final magnetic gel properties. Herein, two different functionalized nanoparticles: citrate-stabilized (14.4 ± 2.6 nm) and lipid-coated (8.9 ± 2.1 nm) magnetic nanoparticles, were used for the formation of dehydropeptide-based supramolecular magnetogels consisting of the ultra-short hydrogelator Cbz-L-Met-Z-ΔPhe-OH, with an assessment of their effect over gel properties. The lipid-coated nanoparticles were distributed along the hydrogel fibers, while citrate-stabilized nanoparticles were aggregated upon gelation, which resulted into a heating efficiency improvement and decrease, respectively. Further, the lipid-coated nanoparticles did not affect drug encapsulation and displayed improved drug release reproducibility compared to citrate-stabilized nanoparticles, despite the latter attaining a stronger AMF-trigger. This report points out that adsorption of nanoparticles to hydrogel fibers, which display domains that improve or do not affect drug encapsulation, can be explored as a means to optimize the development of supramolecular magnetogels to advance theranostic applications.

Magnetically Induced CO2 Methanation Using Exchange-Coupled Spinel Ferrites in Cuboctahedron-Shaped Nanocrystals.

Magnetically induced catalysis can be promoted taking advantage of optimal heating properties from the magnetic nanoparticles to be employed. However, when unprotected, these heating agents that are usually air-sensitive, get sintered under the harsh catalytic conditions. In this context, we present, to the best of our knowledge, the first example of air-stable magnetic nanoparticles that: 1) show excellent performance as heating agents in the CO2 methanation catalyzed by Ni/SiRAlOx, with CH4 yields above 95 %, and 2) do not sinter under reaction conditions. To attain both characteristics we demonstrate, first the exchange-coupled magnetic approach as an alternative and effective way to tune the magnetic response and heating efficiency, and second, the chemical stability of cuboctahedron-shaped core-shell hard CoFe2 O4 -soft Fe3 O4 nanoparticles.

Microswimmers with Heat Delivery Capacity for 3D Cell Spheroid Penetration.

Micro- and nanoswimmers are a fast emerging concept that changes how colloidal and biological systems interact. They can support drug delivery vehicles, assist in crossing biological barriers, or improve diagnostics. We report microswimmers that employ collagen, a major extracellular matrix (ECM) constituent, as fuel and that have the ability to deliver heat via incorporated magnetic nanoparticles when exposed to an alternating magnetic field (AMF). Their assembly and heating properties are outlined followed by the assessment of their calcium-triggered mobility in aqueous solution and collagen gels. It is illustrated that the swimmers in collagen gel in the presence of a steep calcium gradient exhibit fast and directed mobility. The experimental data are supported with theoretical considerations. Finally, the successful penetration of the swimmers into 3D cell spheroids is shown, and upon exposure to an AMF, the cell viability is impaired due to the locally delivered heat. This report illustrates an opportunity to employ swimmers to enhance tissue penetration for cargo delivery via controlled interaction with the ECM.

Titanate Nanowires as One-Dimensional Hot Spot Generators for Broadband Au-TiO2 Photocatalysis.

Metal-semiconductor nanocomposites have become interesting materials for the development of new photocatalytic hybrids. Along these lines, plasmonic nanoparticles have proven to be particularly efficient photosensitizers due to their ability to transfer plasmonic hot electrons onto large bandgap semiconductors such as TiO2, thus extending the activity of the latter into a broader range of the electromagnetic spectrum. The extent of this photosensitization process can be substantially enhanced in those geometries in which high electromagnetic fields are created at the metal-semiconductor interface. In this manner, the formation of plasmonic hot spots can be used as a versatile tool to engineer the photosensitization process in this family of hybrid materials. Herein, we introduce the use of titanate nanowires as ideal substrates for the assembly of Au nanorods and TiO2 nanoparticles, leading to the formation of robust hybrids with improved photocatalytic properties. Our approach shows that the correct choice of the individual units together with their rational assembly are of paramount importance in the development of complex nanostructures with advanced functionalities.

Clusters of Magnetite-Maghemite Nanocrystals with a Chemically-Tailored Average Diameter.

Clusters of magnetic nanocrystals are very advantageous if keeping the superparamagnetic state of the individual nanocrystals while taking advantage of a large total magnetic moment, as very convenient in sensing, catalysis and bio-related applications. Herein, we demonstrate how the molecular weight of poly(ethylene glycol) exerts a dominant role in controlling the final size of the clusters and individual crystallites forming them, which delineate the final magnetic properties and their potential applications.

Spontaneous Formation of Cold-Welded Plasmonic Nanoassemblies with Refracted Shapes for Intense Raman Scattering.

Nanostructures with concave shapes made from continuous segments of plasmonic metals are known to dramatically enhance Raman scattering. Their synthesis in solutions is hindered, however, by their thermodynamic instability due to large surface area and high curvature of refracted geometries with nanoscale dimensions. Herein, we show that nanostructures with concave geometries can spontaneously form via self-organization of gold nanoparticles (NPs) at the air-water interface. The weakly bound surface ligands on the particle surface make possible their spontaneous accumulation and self-assembly at the air-water interface, forming monoparticulate films. Upon heating to 80 °C, the NPs further assemble into concave nanostructures where NPs are cold-welded to each other. Furthermore, the nanoassemblies effectively adsorb molecular analytes during their migration from the bulk solution to the surface where they can be probed by laser spectroscopies. We demonstrate that these films with local concentration of analytes increased by orders of magnitude and favorable plasmonic shapes can be exploited for surface-enhanced Raman scattering for high-sensitivity analysis of aliphatic molecules.

Raman spectroscopy to unravel the magnetic properties of iron oxide nanocrystals for bio-related applications.

Iron oxide nanocrystals have become a versatile tool in biomedicine because of their low cytotoxicity while offering a wide range of tuneable magnetic properties that may be implemented in magnetic separation, drug and heat delivery and bioimaging. These capabilities rely on the unique magnetic features obtained when combining different iron oxide phases, so that an important portfolio of magnetic properties can be attained by the rational design of multicomponent nanocrystals. In this context, Raman spectroscopy is an invaluable and fast-performance tool to gain insight into the different phases forming part of the nanocrystals to be used, allowing correlation of the magnetic properties with the envisaged bio-related applications.

Shaping iron oxide nanocrystals for magnetic separation applications.

Iron oxide nanostructures are attractive for a variety of bio-related applications given their wide range of magnetic properties. Here, we report on the study of the magnetophoretic mobility of octapod-shaped nanocrystals, which we relate to stoichiometry, quality and elongation in the 111 direction of these cubic structures. This special morphology combines magnetocrystalline anisotropies, increases shape anisotropy and hinders the formation of an epitaxial wüstite-magnetite interface. As a result, one obtains nanocrystals with large magnetic susceptibility and small coercivity, that is, with optimum characteristics for magnetic guidance, separation, and drug delivery, due to the increased magnetophoretic mobility displayed.

Double-Fueled Janus Swimmers with Magnetotactic Behavior.

Self-propelled particles attract a great deal of attention due to the auspicious range of applications for which nanobots can be used. In a biomedical context, self-propelled swimmers hold promise to autonomously navigate to a desired location in an attempt to counteract cell/tissue defects either by releasing drugs or by performing surgical tasks. The vast majority of prior reports deal with single engine assemblies, often utilizing fuel molecules which are considered to be highly cytotoxic. Herein, we introduce two engines: (1) a motor which couples enzymes (i.e., glucose oxidase) and inorganic nanoparticles (i.e., platinum nanoparticles) to gain power and (2) a peptide-fueled trypsin motor. We demonstrate that both engines can induce enhanced diffusion properties of (Janus) particles using bioavailable and completely harmless fuel molecules. By combining both engines on the same carrier, we show self-propelled particles employing two independent engines, using two different fuels. A collaborative enhancement of the swimmer's diffusion properties upon powering-up both engines simultaneously is observed. Additionally, the incorporation of magnetic nanoparticles allows for the swimmer to move in a magnetic gradient upon applying an external magnetic field, yielding in directional motion of the double-fueled particles. These multiple-fueled biocompatible swimmers are a significant contribution to make them applicable in a biomedical context.

Solvothermally Driven Mn Doping and Clustering of Iron Oxide Nanoparticles for Heat Delivery Applications.

Direct interactions between nanoparticles of Mn-doped magnetite or maghemite (clearly differentiated by Raman spectroscopy) grouped in spherical clusters minimize the effect related to their characteristic magnetic dead layer at the surface. Hence, the clustering process jointly with the manganese doping renders these ferrite nanostructures very attractive as displaying increased saturation magnetization, offering, consequently, outstanding values of the specific absorption rate (SAR) for heat delivery. The whole picture for bio-related applications has been considered, with issues related to magnetic manipulation, colloidal stability, and biocompatibility.

Enhancing the Exploitation of Functional Nanomaterials through Spatial Confinement: The Case of Inorganic Submicrometer Capsules.

Hollow inorganic nanostructures have attracted much interest in the last few years due to their many applications in different areas of science and technology. In this Feature Article, we overview part of our current work concerning the collective use of plasmonic and magnetic nanoparticles located in voided nanostructures and explore the more specific operational issues that should be taken into account in the design of inorganic nanocapsules. Along these lines, we focus our attention on the applications of silica-based submicrometer capsules aiming to stress the importance of creating nanocavities in order to further exploit the great potential of these functional nanomaterials. Additionally, we will examine some of the recent research on this topic and try to establish a perspective for future developments in this area.

Interplay of chemical structure and magnetic order coupling at the interface between Cr2O3 and Fe3O4 in hybrid nanocomposites.

Hybrid nanocomposites based on ferrimagnetic (FiM) Fe3O4 and magnetoelectric antiferromagnetic (AFM) Cr2O3 nanocrystals were synthesized to offer a particular three-dimensional (3D) interface between the two oxides. This interface favours an intermixing process (demonstrated by combining Raman spectroscopy and magnetization measurements) that determines the final magnetic behavior.