Search

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-β 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. [ABSTRACT FROM AUTHOR]

Previous studies demonstrated sex-related differences in several areas of the human brain, including patterns of brain activation in males and females when observing their own bodies and faces (versus other bodies/faces or morphed versions of themselves), but a complex paradigm touching multiple aspects of embodied self-identity is still lacking. We enrolled 24 healthy individuals (12 M, 12 F) in 3 different fMRI experiments: the vision of prototypical body silhouettes, the vision of static images of the face of the participants morphed with prototypical male and female faces, the vision of short videos showing the dynamic transformation of the morphing. We found differential sexual activations in areas linked to self-identity and to the ability to attribute mental states: In Experiment 1, the male group activated more the bilateral thalamus when looking at sex congruent body images, while the female group activated more the middle and inferior temporal gyrus. In Experiment 2, the male group activated more the supplementary motor area when looking at their faces; the female group activated more the dorsomedial prefrontal cortex (dmPFC). In Experiment 3, the female group activated more the dmPFC when observing either the feminization or the masculinization of their face. The defeminization produced more activations in females in the left superior parietal lobule and middle occipital gyrus. The performance of all classifiers built using single ROIs exceeded chance level, reaching an area under the ROC curves > 0.85 in some cases (notably, for Experiment 2 using the V1 ROI). The results of the fMRI tasks showed good agreement with previously published studies, even if our sample size was small. Therefore, our functional MRI protocol showed significantly different patterns of activation in males and females, but further research is needed both to investigate the gender-related differences in activation when observing a morphing of their face/body, and to validate our paradigm using a larger sample. [ABSTRACT FROM AUTHOR]

One of the most challenging goals in pharmacological research is overcoming the Blood Brain Barrier (BBB) to deliver drugs to the Central Nervous System (CNS). The use of physical means, such as steady and alternating magnetic fields to drive nanocarriers with proper magnetic characteristics may prove to be a useful strategy. The present review aims at providing an up-to-date picture of the applications of magnetic-driven nanotheranostics agents to the CNS. Although well consolidated on physical ground, some of the techniques described herein are still under investigation on in vitro or in silico models, while others have already entered in--or are close to--clinical validation. The review provides a concise overview of the physical principles underlying the behavior of magnetic nanoparticles (MNPs) interacting with an external magnetic field. Thereafter we describe the physiological pathways by which a substance can reach the brain from the bloodstream and then we focus on those MNP applications that aim at a nondestructive crossing of the BBB such as static magnetic fields to facilitate the passage of drugs and alternating magnetic fields to increment BBB permeability by magnetic heating. In conclusion, we briefly cite the most notable biomedical applications of MNPs and some relevant remarks about their safety and potential toxicity. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Magnetic Oxygen-Loaded Nanobubbles (MOLNBs), manufactured by adding Superparamagnetic Iron Oxide Nanoparticles (SPIONs) on the surface of polymeric nanobubbles, are investigated as theranostic carriers for delivering oxygen and chemotherapy to brain tumors. Physicochemical and cyto-toxicological properties and in vitro internalization by human brain microvascular endothelial cells as well as the motion of MOLNBs in a static magnetic field were investigated. MOLNBs are safe oxygen-loaded vectors able to overcome the brain membranes and drivable through the Central Nervous System (CNS) to deliver their cargoes to specific sites of interest. In addition, MOLNBs are monitorable either via Magnetic Resonance Imaging (MRI) or Ultrasound (US) sonography. MOLNBs can find application in targeting brain tumors since they can enhance conventional radiotherapy and deliver chemotherapy being driven by ad hoc tailored magnetic fields under MRI and/or US monitoring. [ABSTRACT FROM AUTHOR]

Magnetic Nanoparticles (MNPs) are of great interest in biomedicine, due to their wide range of applications. During recent years, one of the most challenging goals is the development of new strategies to finely tune the unique properties of MNPs, in order to improve their effectiveness in the biomedical field. This review provides an up-to-date overview of the methods of synthesis and functionalization of MNPs focusing on Iron Oxide Nanoparticles (IONPs). Firstly, synthesis strategies for fabricating IONPs of different composition, sizes, shapes, and structures are outlined. We describe the close link between physicochemical properties and magnetic characterization, essential to developing innovative and powerful magnetic-driven nanocarriers. In conclusion, we provide a complete background of IONPs functionalization, safety, and applications for the treatment of Central Nervous System disorders. [ABSTRACT FROM AUTHOR]

Previous studies demonstrated sex-related differences in several areas of the human brain, including patterns of brain activation in males and females when observing their own bodies and faces (versus other bodies/faces or morphed versions of themselves), but a complex paradigm touching multiple aspects of embodied self-identity is still lacking. We enrolled 24 healthy individuals (12 M, 12 F) in 3 different fMRI experiments: the vision of prototypical body silhouettes, the vision of static images of the face of the participants morphed with prototypical male and female faces, the vision of short videos showing the dynamic transformation of the morphing. We found differential sexual activations in areas linked to self-identity and to the ability to attribute mental states: In Experiment 1, the male group activated more the bilateral thalamus when looking at sex congruent body images, while the female group activated more the middle and inferior temporal gyrus. In Experiment 2, the male group activated more the supplementary motor area when looking at their faces; the female group activated more the dorsomedial prefrontal cortex (dmPFC). In Experiment 3, the female group activated more the dmPFC when observing either the feminization or the masculinization of their face. The defeminization produced more activations in females in the left superior parietal lobule and middle occipital gyrus. The performance of all classifiers built using single ROIs exceeded chance level, reaching an area under the ROC curves > 0.85 in some cases (notably, for Experiment 2 using the V1 ROI). The results of the fMRI tasks showed good agreement with previously published studies, even if our sample size was small. Therefore, our functional MRI protocol showed significantly different patterns of activation in males and females, but further research is needed both to investigate the gender-related differences in activation when observing a morphing of their face/body, and to validate our paradigm using a larger sample.

One of the most challenging goals in pharmacological research is overcoming the Blood Brain Barrier (BBB) to deliver drugs to the Central Nervous System (CNS). The use of physical means, such as steady and alternating magnetic fields to drive nanocarriers with proper magnetic characteristics may prove to be a useful strategy. The present review aims at providing an up-to-date picture of the applications of magnetic-driven nanotheranostics agents to the CNS. Although well consolidated on physical ground, some of the techniques described herein are still under investigation on in vitro or in silico models, while others have already entered in-or are close to-clinical validation. The review provides a concise overview of the physical principles underlying the behavior of magnetic nanoparticles (MNPs) interacting with an external magnetic field. Thereafter we describe the physiological pathways by which a substance can reach the brain from the bloodstream and then we focus on those MNP applications that aim at a nondestructive crossing of the BBB such as static magnetic fields to facilitate the passage of drugs and alternating magnetic fields to increment BBB permeability by magnetic heating. In conclusion, we briefly cite the most notable biomedical applications of MNPs and some relevant remarks about their safety and potential toxicity., Competing Interests: The authors declare no conflict of interest.