Developing Iron Nanochelating Agents: Preliminary Investigation of Effectiveness and Safety for Central Nervous System Applications.

Excessive iron levels are believed to contribute to the development of neurodegenerative disorders by promoting oxidative stress and harmful protein clustering. Novel chelation treatments that can effectively remove excess iron while minimizing negative effects on the nervous system are being explored. This study focuses on the creation and evaluation of innovative nanobubble (NB) formulations, shelled with various polymers such as glycol-chitosan (GC) and glycol-chitosan conjugated with deferoxamine (DFO), to enhance their ability to bind iron. Various methods were used to evaluate their physical and chemical properties, chelation capacity in diverse iron solutions and impact on reactive oxygen species (ROS). Notably, the GC-DFO NBs demonstrated the ability to decrease amyloid-ß protein misfolding caused by iron. To assess potential toxicity, in vitro cytotoxicity testing was conducted using organotypic brain cultures from the substantia nigra, revealing no adverse effects at appropriate concentrations. Additionally, the impact of NBs on spontaneous electrical signaling in hippocampal neurons was examined. Our findings suggest a novel nanochelation approach utilizing DFO-conjugated NBs for the removal of excess iron in cerebral regions, potentially preventing neurotoxic effects.

Magnetic Shape-Memory Heuslers Turn to Bio: Cytocompatibility of Ni-Mn-Ga Films and Biomedical Perspective.

Magnetic shape-memory (MSM) Heuslers have attracted great attention in recent years for both caloric and magnetomechanical applications. Thanks to their multifunctional properties, they are also promising for a vast variety of biomedical applications. However, this topic has been rarely investigated so far. In this communication, we present the first report on the absence of cytotoxicity of MSM Heuslers in Ni-Mn-Ga epitaxial thin films and the perspective toward bioapplications. Qualitative and quantitative biological characterizations reveal that Ni-Mn-Ga films can promote the adhesion and proliferation of human fibroblasts without eliciting any cytotoxic effect. Additionally, our findings show that the morphology, composition, microstructure, phase transformation, and magnetic characteristics of the films are well preserved after the biological treatments, making the material a promising candidate for further investigations.

Step-by-Step Design of New Theranostic Nanoformulations: Multifunctional Nanovectors for Radio-Chemo-Hyperthermic Therapy under Physical Targeting.

While investigating the possible synergistic effect of the conventional anticancer therapies, which, taken individually, are often ineffective against critical tumors, such as central nervous system (CNS) ones, the design of a theranostic nanovector able to carry and deliver chemotherapy drugs and magnetic hyperthermic agents to the target radiosensitizers (oxygen) was pursued. Alongside the original formulation of polymeric biodegradable oxygen-loaded nanostructures, their properties were fine-tuned to optimize their ability to conjugate therapeutic doses of drugs (doxorubicin) or antitumoral natural substances (curcumin). Oxygen-loaded nanostructures (diameter = 251 ± 13 nm, ζ potential = -29 ± 5 mV) were finally decorated with superparamagnetic iron oxide nanoparticles (SPIONs, diameter = 18 ± 3 nm, ζ potential = 14 ± 4 mV), producing stable, effective and non-agglomerating magnetic nanovectors (diameter = 279 ± 17 nm, ζ potential = -18 ± 7 mV), which could potentially target the tumoral tissues under magnetic driving and are monitorable either by US or MRI imaging.

Following the Martensitic Configuration Footprints in the Transition Route of Ni-Mn-Ga Magnetic Shape Memory Films: Insight into the Role of Twin Boundaries and Interfaces.

Magnetic shape memory Heuslers have a great potential for their exploitation in next-generation cooling devices and actuating systems, due to their "giant" caloric and thermo/magnetomechanical effects arising from the combination of magnetic order and a martensitic transition. Thermal hysteresis, broad transition range, and twinning stress are among the major obstacles preventing the full exploitation of these materials in applications. Using Ni-Mn-Ga seven-modulated epitaxial thin films as a model system, we investigated the possible links between the phase transition and the details of the twin variants configuration in the martensitic phase. We explored the crystallographic relations between the martensitic variants from the atomic-scale to the micro-scale through high-resolution techniques and combined this information with the direct observation of the evolution of martensitic twin variants vs. temperature. Based on our multiscale investigation, we propose a route for the martensitic phase transition, in which the interfaces between different colonies of twins play the major role of initiators for both the forward and reverse phase transition. Linking the martensitic transition to the martensitic configuration sheds light onto the possible mechanisms influencing the transition and paves the way towards microstructure engineering for the full exploitation of shape memory Heuslers in different applications.

Magnetically responsive polycaprolactone nanocarriers for application in the biomedical field: magnetic hyperthermia, magnetic resonance imaging, and magnetic drug delivery.

There are huge demands on multifunctional nanocarriers to be used in nanomedicine. Herein, we present a simple and efficient method for the preparation of multifunctional magnetically responsive polymeric-based nanocarriers optimized for biomedical applications. The hybrid delivery system is composed of drug-loaded polymer nanoparticles (poly(caprolactone), PCL) coated with a multilayer shell of polyglutamic acid (PGA) and superparamagnetic iron oxide nanoparticles (SPIONs), which are known as bio-acceptable components. The PCL nanocarriers with a model anticancer drug (Paclitaxel, PTX) were formed by the spontaneous emulsification solvent evaporation (SESE) method, while the magnetically responsive multilayer shell was formed via the layer-by-layer (LbL) method. As a result, we obtained magnetically responsive polycaprolactone nanocarriers (MN-PCL NCs) with an average size of about 120 nm. Using the 9.4 T preclinical magnetic resonance imaging (MRI) scanner we confirmed, that obtained MN-PCL NCs can be successfully used as a MRI-detectable drug delivery system. The magnetic hyperthermia effect of the MN-PCL NCs was demonstrated by applying a 25 mT radio-frequency (f = 429 kHz) alternating magnetic field. We found a Specific Absorption Rate (SAR) of 55 W g-1. The conducted research fulfills the first step of investigation for biomedical application, which is mandatory for the planning of any in vitro and in vivo studies.

Superparamagnetic Oxygen-Loaded Nanobubbles to Enhance Tumor Oxygenation During Hyperthermia.

Tumor oxygenation is a critical issue for enhancing radiotherapy (RT) effectiveness. Alternating RT with hyperthermia improves tumor radiosensitivity by inducing a massive vasodilation of the neoangiogenic vasculature provided the whole tumor is properly heated. The aim of this work was to develop superparamagnetic oxygen-loaded nanobubbles (MOLNBs) as innovative theranostic hyperthermic agents to potentiate tumor oxygenation by direct intracellular oxygen administration. Magnetic oxygen-loaded nanobubbles were obtained by functionalizing dextran-shelled and perfluoropentane-cored nanobubbles with superparamagnetic iron oxide nanoparticles. Magnetic oxygen-loaded nanobubbles with sizes of about 380 nm were manufactured, and they were able to store oxygen and in vitro release it with prolonged kinetics. In vitro investigation showed that MOLNBs can increase tissue temperature when exposed to radiofrequency magnetic fields. Moreover, they are easily internalized by tumor cells, herein releasing oxygen with a sustained kinetics. In conclusion, MOLNBs can be considered a multimodal theranostic platform since, beyond their nature of contrast agent for magnetic resonance imaging due to magnetic characteristics, they showed echogenic properties and can be visualized using medical ultrasound.

Magnetic Shape Memory Turns to Nano: Microstructure Controlled Actuation of Free-Standing Nanodisks.

Magnetic shape memory materials hold a great promise for next-generation actuation devices and systems for energy conversion, thanks to the intimate coupling between structure and magnetism in their martensitic phase. Here novel magnetic shape memory free-standing nanodisks are proposed, proving that the lack of the substrate constrains enables the exploitation of new microstructure-controlled actuation mechanisms by the combined application of different stimuli-i.e., temperature and magnetic field. The results show that a reversible areal strain (up to 5.5%) can be achieved and tuned in intensity and sign (i.e., areal contraction or expansion) by the application of a magnetic field. The mechanisms at the basis of the actuation are investigated by experiments performed at different length scales and directly visualized by several electron microscopy techniques, including electron holography, showing that thermo/magnetomechanical properties can be optimized by engineering the martensitic microstructure through epitaxial growth and lateral confinement. These findings represent a step forward toward the development of a new class of temperature-field controlled nanoactuators and smart nanomaterials.

Hybrid Polyelectrolyte/Fe3O4 Nanocapsules for Hyperthermia Applications.

We validated here the applicability to hyperthermia treatment of magnetic nanocapsules prepared by the sequential layer-by-layer adsorption of polyelectrolytes and magnetic, Fe3O4 nanoparticles. For the shell preparation around a nanodroplet liquid core, biocompatible polyelectrolytes were used: poly l-lysine as the polycation and poly glutamic acid as the polyanion. The hyperthermia effect was demonstrated by applying the radio frequency (rf) magnetic field with maximum fields H up to 0.025 T and frequencies up to 430 kHz; we found sizable heating effects, with a heating rate up to 0.46 °C/min. We also found effects of irradiation on capsules' morphology that indicated their disruption, thus suggesting their potential use as nanocarriers of drugs that can be locally released on demand. Therefore, these magnetically responsive nanocapsules could be a promising platform for multifunctional biomedical applications such as the controlled release of pharmaceuticals in combination with hyperthermia treatment.

Magnetic Nanoparticles-Loaded Physarum polycephalum: Directed Growth and Particles Distribution.

Slime mold Physarum polycephalum is a single cell visible by an unaided eye. The slime mold optimizes its network of protoplasmic tubes to minimize expose to repellents and maximize expose to attractants and to make efficient transportation of nutrients. These properties of P. polycephalum, together with simplicity of its handling and culturing, make it a priceless substrate for designing novel sensing, computing and actuating architectures in living amorphous biological substrate. We demonstrate that, by loading Physarum with magnetic particles and positioning it in a magnetic field, we can, in principle, impose analog control procedures to precisely route active growing zones of slime mold and shape topology of its protoplasmic networks.

Achieving giant magnetically induced reorientation of martensitic variants in magnetic shape-memory Ni-Mn-Ga Films by microstructure engineering.

Giant magnetically induced twin variant reorientation, comparable in intensity with bulk single crystals, is obtained in epitaxial magnetic shape-memory thin films. It is found to be tunable in intensity and spatial response by the fine control of microstructural patterns at the nanoscopic and microscopic scales. A thorough experimental study (including electron holography) allows a multiscale comprehension of the phenomenon.

Magnetic nanoparticles-loaded Physarum polycephalum: Directed growth and particles distribution.

Slime mold Physarum polycephalum is a single cell visible by an unaided eye. The slime mold optimizes its network of protoplasmic tubes to minimize expose to repellents and maximize expose to attractants and to make efficient transportation of nutrients. These properties of P. polycephalum, together with simplicity of its handling and culturing, make it a priceless substrate for designing novel sensing, computing and actuating architectures in living amorphous biological substrate. We demonstrate that, by loading Physarum with magnetic particles and positioning it in a magnetic field, we can, in principle, impose analog control procedures to precisely route active growing zones of slime mold and shape topology of its protoplasmic networks.

Magnetic nanoparticles-loaded Physarum polycephalum: Directed growth and particles distribution.

Slime mold Physarum polycephalum is a single cell visible by an unaided eye. The slime mold optimizes its network of protoplasmic tubes to minimize expose to repellents and maximize expose to attractants and to make efficient transportation of nutrients. These properties of P. polycephalum, together with simplicity of its handling and culturing, make it a priceless substrate for designing novel sensing, computing and actuating architectures in living amorphous biological substrate. We demonstrate that, by loading Physarum with magnetic particles and positioning it in a magnetic field, we can, in principle, impose analog control procedures to precisely route active growing zones of slime mold and shape topology of its protoplasmic networks.