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Background: Treating mitochondrial dysfunction is a promising approach for the treatment of post-stroke cognitive impairment (PSCI). HuMSC-derived exosomes (H-Ex) have shown powerful therapeutic effects in improving mitochondrial function, but the specific effects are unclear and its brain tissue targeting needs to be further optimized. Results: In this study, we found that H-Ex can improve mitochondrial dysfunction of neurons and significantly enhance the cognitive behavior performance of MCAO mice in OGD/R-induced SHSY5Y cells and MCAO mouse models. Based on this, we have developed an exosome delivery system loaded with superparamagnetic iron oxide nanoparticles (Spion-Ex) that can effectively penetrate the blood-brain barrier (BBB). The research results showed that under magnetic attraction, Spion-Ex can more effectively target the brain tissue and significantly improve mitochondrial function of neurons after stroke. Meanwhile, we further confirmed that miR-1228-5p is a key factor for H-Ex to improve mitochondrial function and cognitive behavior both in vivo and in vitro. The specific mechanism is that the increase of miR-1228-5p mediated by H-Ex can inhibit the expression of TRAF6 and activate the TRAF6-NADPH oxidase 1 (NOX1) pathway, thereby exerting protective effects against oxidative damage. More importantly, we found that under magnetic attraction, Spion-Ex exhibited excellent cognitive improvement effects by delivering miR-1228-5p. Conclusions: Our research found that H-Ex has a good therapeutic effect on PSCI by increasing the expression of miR-1228-5p in PSCI, while H-Ex loaded with Spion-Ex exhibited more excellent effects on improving mitochondrial function and cognitive impairment under magnetic attraction, which can be used as a novel strategy for the treatment of PSCI. [ABSTRACT FROM AUTHOR]

To tailor superparamagnetic iron oxide nanoparticles (SPIONs) to the specific needs of diverse application fields, it is essential to understand not only their intrinsic properties but also their interactions with each other. Theoretical models predicting/explaining the magnetization behavior of macroscopic samples containing millions of SPIONs are intricate due to the complexity of the underlying relaxation mechanisms in alternating fields. This study introduces supraparticles (SPs) as model architectures to empirically investigate magnetic interactions within and between large SPION clusters (>100 nanoparticles (NPs)). For this purpose, NP dispersions containing SPIONs and silica (SiO2)NPs as non‐magnetic building blocks are spray‐dried to form binary SPs. Selective salt‐induced agglomeration of the two building block types before spray‐drying is utilized to tailor SP architectures, including control over SPION cluster size, shape, and proximity. Magnetic particle spectroscopy (MPS), operating under ambient conditions, reveals altered magnetization behavior for different cluster structures. Not only the nearest SPION neighbors, but the whole cluster structure up to several micrometers is decisive for the magnetization behavior. This highlights the importance of long‐range magnetic interactions. This work presents a versatile approach for designing model architectures to advance empirical interaction studies between SPIONs in macroscopic samples. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs) have significant therapeutic potential and their use requires in-depth studies to better understand their effects. Labeling cells with superparamagnetic iron oxide nanoparticles allows real-time monitoring of their location, migration, and fate post-transplantation. This study aimed to investigate the efficacy and cytotoxicity of magnetic–fluorescent nanoparticles in human adipose tissue-derived mesenchymal stem cells (hADSCs). The efficacy of Molday ION rhodamine B (MIRB) labeling in hADSCs was evaluated and their biocompatibility was assessed using various techniques and differentiation assays. Prussian blue and fluorescence staining confirmed that 100% of the cells were labeled with MIRB and this labeling persisted for at least 3 days. Transmission electron microscopy revealed the internalization and clustering of the nanoparticles on the outer surface of the cell membrane. The viability assay showed increased cell viability 3 days after nanoparticle exposure. Cell counts were higher in the MIRB-treated group compared to the control group at 3 and 5 days and an increased cell proliferation rate was observed at 3 days post-exposure. Adipogenic, osteogenic, and chondrogenic differentiation was successfully achieved in all groups, with MIRB-treated cells showing an enhanced differentiation rate into adipocytes and osteocytes. MIRB was efficiently internalized by hADSCs but induced changes in cellular behavior due to the increased cell proliferation rate. [ABSTRACT FROM AUTHOR]

Abstract Background Treating mitochondrial dysfunction is a promising approach for the treatment of post-stroke cognitive impairment (PSCI). HuMSC-derived exosomes (H-Ex) have shown powerful therapeutic effects in improving mitochondrial function, but the specific effects are unclear and its brain tissue targeting needs to be further optimized. Results In this study, we found that H-Ex can improve mitochondrial dysfunction of neurons and significantly enhance the cognitive behavior performance of MCAO mice in OGD/R-induced SHSY5Y cells and MCAO mouse models. Based on this, we have developed an exosome delivery system loaded with superparamagnetic iron oxide nanoparticles (Spion-Ex) that can effectively penetrate the blood-brain barrier (BBB). The research results showed that under magnetic attraction, Spion-Ex can more effectively target the brain tissue and significantly improve mitochondrial function of neurons after stroke. Meanwhile, we further confirmed that miR-1228-5p is a key factor for H-Ex to improve mitochondrial function and cognitive behavior both in vivo and in vitro. The specific mechanism is that the increase of miR-1228-5p mediated by H-Ex can inhibit the expression of TRAF6 and activate the TRAF6-NADPH oxidase 1 (NOX1) pathway, thereby exerting protective effects against oxidative damage. More importantly, we found that under magnetic attraction, Spion-Ex exhibited excellent cognitive improvement effects by delivering miR-1228-5p. Conclusions Our research found that H-Ex has a good therapeutic effect on PSCI by increasing the expression of miR-1228-5p in PSCI, while H-Ex loaded with Spion-Ex exhibited more excellent effects on improving mitochondrial function and cognitive impairment under magnetic attraction, which can be used as a novel strategy for the treatment of PSCI.

Juan Li,1,* Ting Zhou,1,* Pei Wang,1,* Ruian Yin,1 Shengqi Zhang,1 Yile Cao,1 Lijuan Zong,1 Ming Xiao,2 Yongjie Zhang,3 Wentao Liu,4 Lingxiao Deng,5 Fei Huang,6 Jianfei Sun,7,* Hongxing Wang1,* 1Department of Rehabilitation Medicine, Zhongda Hospital Southeast University, Nanjing, 210024, People’s Republic of China; 2Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, 211166, People’s Republic of China; 3Department of Human Anatomy, Nanjing Medical University, Nanjing, 211166, People’s Republic of China; 4Department of Pharmacology, Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, 211166, People’s Republic of China; 5Department of Neurological Surgery, Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Indianapolis, IN, 46202-2266, USA; 6Institute of Neurobiology, Binzhou Medical University, Yantai, 264003, People’s Republic of China; 7State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory of Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210009, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianfei Sun, State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory of Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210009, People’s Republic of China, Email sunzaghi@seu.edu.cn Hongxing Wang, Department of Rehabilitation Medicine, Southeast University Zhongda Hospital, Nanjing, 210024, People’s Republic of China, Email 101012648@seu.edu.cnBackground: Gigantocellular reticular nucleus (GRNs) executes a vital role in locomotor recovery after spinal cord injury. However, due to its unique anatomical location deep within the brainstem, intervening in GRNs for spinal cord injury research is challenging. To address this problem, this study adopted an extracorporeal magnetic stimulation system to observe the effects of selective magnetic stimulation of GRNs with iron oxide nanoparticles combined treadmill training on locomotor recovery after spinal cord injury, and explored the possible mechanisms.Methods: Superparamagnetic iron oxide (SPIO) nanoparticles were stereotactically injected into bilateral GRNs of mice with moderate T10 spinal cord contusion. Eight-week selective magnetic stimulation produced by extracorporeal magnetic stimulation system (MSS) combined with treadmill training was adopted for the animals from one week after surgery. Locomotor function of mice was evaluated by the Basso Mouse Scale, Grid-walking test and Treadscan analysis. Brain MRI, anterograde virus tracer and immunofluorescence staining were applied to observe the tissue compatibility of SPIO in GRNs, trace GRNs’ projections and evaluate neurotransmitters’ expression in spinal cord respectively. Motor-evoked potentials and H reflex were collected for assessing the integrity of cortical spinal tract and the excitation of motor neurons in anterior horn.Results: (1) SPIO persisted in GRNs for a minimum of 24 weeks without inducing apoptosis of GRN cells, and degraded slowly over time. (2) MSS-enabled treadmill training dramatically improved locomotor performances of injured mice, and promoted cortico-reticulo-spinal circuit reorganization. (3) MSS-enabled treadmill training took superimposed roles through both activating GRNs to drive more projections of GRNs across lesion site and rebalancing neurotransmitters’ expression in anterior horn of lumbar spinal cord.Conclusion: These results indicate that selective MSS intervention of GRNs potentially serves as an innovative strategy to promote more spared fibers of GRNs across lesion site and rebalance neurotransmitters’ expression after spinal cord injury, paving the way for the structural remodeling of neural systems collaborating with exercise training, thus ultimately contributing to the reconstruction of cortico-reticulo-spinal circuit. Keywords: gigantocellular reticular nucleus, locomotion, magnetic stimulation, spinal cord injury, superparamagnetic iron oxide nanoparticles, treadmill training

Introduction: The study aimed to systematically enhance the fabrication process of flurbiprofen-loaded bilosomes (FSB) using Quality by Design (QbD) principles and Design of Experiments (DOE). The objective was to develop an optimized formulation with improved entrapment efficiency and targeted drug delivery capabilities. Methods: The optimization process involved applying QbD principles and DOE to achieve the desired formulation characteristics. Superparamagnetic iron oxide nanoparticles (SPIONs) were incorporated to impart magnetic responsiveness. The size, entrapment efficiency, morphology, and in vitro release patterns of the FSB formulation were evaluated. Additionally, an in situ forming hydrogel incorporating FSB was developed, with its gelation time and drug release kinetics assessed. In vivo studies were conducted on osteoarthritic rats to evaluate the efficacy of the FSB-loaded hydrogel. Results: The optimized FSB formulation yielded particles with a size of 453.60 nm and an entrapment efficiency of 91.57%. The incorporation of SPIONs enhanced magnetic responsiveness. Morphological evaluations and in vitro release studies confirmed the structural integrity and sustained release characteristics of the FSB formulation. The in situ forming hydrogel exhibited a rapid gelation time of approximately 40 ± 1.8 s and controlled drug release kinetics. In vivo studies demonstrated a 27.83% reduction in joint inflammation and an 85% improvement in locomotor activity in osteoarthritic rats treated with FSB-loaded hydrogel. Discussion: This comprehensive investigation highlights the potential of FSB as a promising targeted drug delivery system for the effective management of osteoarthritis. The use of QbD and DOE in the formulation process, along with the integration of SPIONs, resulted in an optimized FSB formulation with enhanced entrapment efficiency and targeted delivery capabilities. The in situ forming hydrogel further supported the formulation's applicability for injectable applications, providing rapid gelation and sustained drug release. The in vivo results corroborate the formulation's efficacy, underscoring its potential for improving the treatment of osteoarthritis. [ABSTRACT FROM AUTHOR]

Superparamagnetic iron oxide nanoparticles (SPIONs) are commonly used as magnetic resonance imaging (MRI) probes/contrast agents in clinical diagnosis because they can significantly improve the sensitivity of MRI. Polymers including natural and synthetic polymers with good biosafety and abundant surface groups are ideal surface coating for SPIONs to overcome their drawbacks such as poor colloidal stability, low relaxivity, and lack of functionality. Several SPIONs' structural properties such as crystal shape and size, charge, shell thickness, and cluster determine their relaxivity, biosafety, and in vivo imaging effect. Therefore, the rational design of SPIONs probes must explore the relationship between polymer structure and SPION properties. In this review, key structural properties of polymers such as surface groups, molecular weight, hydrophilicity, and grafting density are discussed for their effects on key properties of SPIONs. Additionally, some special polysaccharides, polypeptides, and antibodies can be used as targeting molecules to improve the imaging specificity of SPIONs, which is also briefly discussed in this review. [ABSTRACT FROM AUTHOR]

Osteoarthritis is a bone and joint condition characterized pathologically by articular cartilage degenerative damage and can develop into a devastating and permanently disabling disorder. This investigation aimed to formulate the anti-inflammatory drug lornoxicam (LOR) into bile salt–enriched vesicles loaded in an in situ forming hydrogel as a potential local treatment of osteoarthritis. This was achieved by formulating LOR-loaded bilosomes that are also loaded with superparamagnetic iron oxide nanoparticles (SPIONs) for intra-muscular (IM) administration to improve joint targeting and localization by applying an external magnet to the joint. A 31.22 full factorial design was employed to develop the bilosomal dispersions and the optimized formula including SPION (LSB) was loaded into a thermosensitive hydrogel. Moreover, in vivo evaluation revealed that the IM administration of LSB combined with the application of an external magnet to the joint reversed carrageen-induced suppression in motor activity and osteoprotegerin by significantly reducing the elevations in mitogen-activated protein kinases, extracellular signal-regulated kinase, and receptor activator of nuclear factor kappa beta/osteoprotegerin expressions. In addition, the histopathological evaluation of knee joint tissues showed a remarkable improvement in the injured joint tissues. The results proved that the developed LSB could be a promising IM drug delivery system for osteoarthritis management. [ABSTRACT FROM AUTHOR]

An increasing number of medications have been explored to treat the progressive and irreversible Alzheimer's disease (AD) that stands as the predominant form of dementia among neurodegenerative ailments. However, assertions about toxic side effects of these drugs are a significant hurdle to overcome, calling for drug-free nanotherapeutics. Herein, a new therapeutic strategy devoid of conventional drugs or other cytotoxic species was developed. The constructed superparamagnetic iron oxide nanoparticles (SPIONs) nanospinners can accrete neurotoxic β-amyloid 42 oligomers (oAβ42) into aggregated magnetic plaques (mpAβ) by mechanical rotating force via remote interaction between nanoparticles and the applied magnetic field. While the cellular uptake of mpAβ attained from the magnetic stirring treatment by neuronal cells is severely limited, the facile phagocytic uptake of mpAβ by microglial cells leads to the polarization of the brain macrophages to M2 phenotype and thus the increased anti-inflammatory responses to the treatment. The SPION stirring treatment protects the AD mice from memory deterioration and maintain cognitive ability as evidenced from both nesting and Barnes maze tests. The examination of the oAβ42 injected brain tissues with the stirring treatment showed significant amelioration of functional impairment of neurons, microglia, astrocytes and oligodendrocytes alongside no obvious tissue damage caused by stirring meanwhile complete degradation of SPION was observed at day 7 after the treatment. The in vitro and animal data of this work strongly corroborate that this new modality of undruggable stirring treatment with SPIONs provides a new feasible strategy for developing novel AD treatments.

Abstract Transcranial magnetic stimulation (TMS) is a neurostimulation device used to modulate brain cortex activity. Our objective was to enhance the therapeutic effectiveness of low-frequency repeated TMS (LF-rTMS) in a rat model of autism spectrum disorder (ASD) induced by prenatal valproic acid (VPA) exposure through the injection of superparamagnetic iron oxide nanoparticles (SPIONs). For the induction of ASD, we administered prenatal VPA (600 mg/kg, I.P.) on the 12.5th day of pregnancy. At postnatal day 30, SPIONs were injected directly into the lateral ventricle of the brain. Subsequently, LF-rTMS treatment was applied for 14 consecutive days. Following the treatment period, behavioral analyses were conducted. At postnatal day 60, brain tissue was extracted, and both biochemical and histological analyses were performed. Our data revealed that prenatal VPA exposure led to behavioral alterations, including changes in social interactions, increased anxiety, and repetitive behavior, along with dysfunction in stress coping strategies. Additionally, we observed reduced levels of SYN, MAP2, and BDNF. These changes were accompanied by a decrease in dendritic spine density in the hippocampal CA1 area. However, LF-rTMS treatment combined with SPIONs successfully reversed these dysfunctions at the behavioral, biochemical, and histological levels, introducing a successful approach for the treatment of ASD.

[Display omitted] • Synthesis of superparamagnetic iron oxide nanoparticles (SPIONs) by thermal decomposition method. • Integrin-targeted SPIONs for mechanotransduction stimulus in osteogenic differentiation. • Remotely activated mechanotransduction via Arg-Gly-Asp (RGD) functionalized SPIONs. • Magnetic mechanotransduction in human bone marrow mesenchymal stem cells (hBM-MSCs) for osteogenic differentiation. • Endocytic mechanisms of SPIONs in hBM-MSCs. • Up-regulation of osteogenic markers after magnetic activation of mechanotransduction in hBM-MSCs. Nowadays, diseases associated with an ageing population, such as osteoporosis, require the development of new biomedical approaches to bone regeneration. In this regard, mechanotransduction has emerged as a discipline within the field of bone tissue engineering. Herein, we have tested the efficacy of superparamagnetic iron oxide nanoparticles (SPIONs), obtained by the thermal decomposition method, with an average size of 13 nm, when exposed to the application of an external magnetic field for mechanotransduction in human bone marrow-derived mesenchymal stem cells (hBM-MSCs). The SPIONs were functionalized with an Arg-Gly-Asp (RGD) peptide as ligand to target integrin receptors on cell membrane and used in colloidal state. Then, a comprehensive and comparative bioanalytical characterization of non-targeted versus targeted SPIONs was performed in terms of biocompatibility, cell uptake pathways and mechanotransduction effect, demonstrating the osteogenic differentiation of hBM-MSCs. A key conclusion derived from this research is that when the magnetic stimulus is applied in the first 30 min of the in vitro assay, i.e. , when the nanoparticles come into contact with the cell membrane surface to initiate endocytic pathways, a successful mechanotransduction effect is observed. Thus, under the application of a magnetic field, there was a significant increase in runt-related transcription factor 2 (Runx2) and alkaline phosphatase (ALP) gene expression as well as ALP activity, when cells were exposed to RGD-functionalized SPIONs, demonstrating osteogenic differentiation. These findings open new expectations for the use of remotely activated mechanotransduction using targeted magnetic colloidal nanoformulations for osteogenic differentiation by drug-free cell therapy using minimally invasive techniques in cases of bone loss. [ABSTRACT FROM AUTHOR]

The aim of this study is the fabrication of unprecedented neuroelectrodes, replete with exceptional biological and electrical attributes. Commencing with the synthesis of polyethylene glycol and polyethyleneimine-modified iron oxide nanoparticles, the grafting of Dimyristoyl phosphatidylcholine was embarked upon to generate DMPC-SPION nanoparticles. Subsequently, the deposition of DMPC-SPIONs onto a nickel–chromium alloy electrode facilitated the inception of an innovative neuroelectrode–DMPC-SPION. A meticulous characterization of DMPC-SPIONs ensued, encompassing zeta potential, infrared spectroscopy, X-ray photoelectron spectroscopy, and X-ray diffraction analyses. Evaluations pertaining to hemolysis and cytotoxicity were conducted to ascertain the biocompatibility and biosafety of DMPC-SPIONs. Ultimately, a comprehensive assessment of the biocompatibility, electrochemical properties, and electrophysiological signal acquisition capabilities of DMPC-SPION neuroelectrodes was undertaken. These findings conclusively affirm the exemplary biocompatibility, electrochemical capabilities, and outstanding capability in recording electrical signals of DMPC-SPION neuroelectrodes, with an astounding 91.4% augmentation in electrode charge and a noteworthy 13% decline in impedance, with peak potentials reaching as high as 171 μV and an impressive signal-to-noise ratio of 15.92. Intriguingly, the novel DMPC-SPION neuroelectrodes herald an innovative pathway towards injury repair as well as the diagnosis and treatment of neurological disorders. [ABSTRACT FROM AUTHOR]

Iron oxide nanoparticles (IONP) have tremendous potential in various applications due to their unique physical and magnetic properties. Controlling synthesis parameters is essential to obtain IONP with desired properties. The influence of stirring rate and reaction time during synthesis of IONP from thermal decomposition of FeOOH on the particle size, crystallinity, and magnetic properties of the IONP were investigated. IONP produced at different reaction times and stirring rates had similar spherical shapes with low polydispersity. Particle size was found to increase from 4.9 nm to 8.6 nm when reaction time increased from 15 to 60 min, with the highest saturation magnetization of 34.3 Am2/kg obtained at 60 min. Stirring rates of 400 and 500 rpm produced IONP with better crystallinity and saturation magnetization than 300 and 600 rpm. The properties of IONP can be tuned by selecting appropriate stirring rates and reaction times during synthesis to suit the intended applications. [ABSTRACT FROM AUTHOR]

Background: Percutaneous microwave ablation (pMWA) is a minimally invasive procedure that uses a microwave antenna placed at the tip of a needle to induce lethal tissue heating. It can treat cancer and other diseases with lower morbidity than conventional surgery, but one major limitation is the lack of control over the heating region around the ablation needle. Superparamagnetic iron oxide nanoparticles have the potential to enhance and control pMWA heating due to their ability to absorb microwave energy and their ease of local delivery. Purpose: The purpose of this study is to experimentally quantify the capabilities of FDA‐approved superparamagnetic iron oxide Feraheme nanoparticles (FHNPs) to enhance and control pMWA heating. This study aims to determine the effectiveness of locally injected FHNPs in increasing the maximum temperature during pMWA and to investigate the ability of FHNPs to create a controlled ablation zone around the pMWA needle. Methods: PMWA was performed using a clinical ablation system at 915 MHz in ex‐vivo porcine liver tissues. Prior to ablation, 50 uL 5 mg/mL FHNP injections were made on one side of the pMWA needle via a 23‐gauge needle. Local temperatures at the FHNP injection site were directly compared to equidistant control sites without FHNP. First, temperatures were compared using directly inserted thermocouples. Next, temperatures were measured non‐invasively using magnetic resonance thermometry (MRT), which enabled comprehensive four‐dimensional (volumetric and temporal) assessment of heating effects relative to nanoparticle distribution, which was quantified using dual‐echo ultrashort echo time (UTE) subtraction MR imaging. Maximum heating within FHNP‐exposed tissues versus control tissues were compared at multiple pMWA energy delivery settings. The ability to generate a controlled asymmetric ablation zone using multiple FHNP injections was also tested. Finally, intra‐procedural MRT‐derived heat maps were correlated with gold standard gross pathology using Dice similarity analysis. Results: Maximum temperatures at the FHNP injection site were significantly higher than control (without FHNP) sites when measured using direct thermocouples (93.1 ± 6.0°C vs. 57.2 ± 8.1°C, p = 0.002) and using non‐invasive MRT (115.6 ± 13.4°C vs. 49.0 ± 10.6°C, p = 0.02). Temperature difference between FHNP‐exposed and control sites correlated with total energy deposition: 66.6 ± 17.6°C, 58.1 ± 8.5°C, and 20.8 ± 9.2°C at high (17.5 ± 2.2 kJ), medium (13.6 ± 1.8 kJ), and low (8.8 ± 1.1 kJ) energies, respectively (all pairwise p < 0.05). Each FHNP injection resulted in a nanoparticle distribution within 0.9 ± 0.2 cm radially of the injection site and a local lethal heating zone confined to within 1.1 ± 0.4 cm radially of the injection epicenter. Multiple injections enabled a controllable, asymmetric ablation zone to be generated around the ablation needle, with maximal ablation radius on the FHNP injection side of 1.6 ± 0.2 cm compared to 0.7 ± 0.2 cm on the non‐FHNP side (p = 0.02). MRT intra‐procedural predicted ablation zone correlated strongly with post procedure gold‐standard gross pathology assessment (Dice similarity 0.9). Conclusions: Locally injected FHNPs significantly enhanced pMWA heating in liver tissues, and were able to control the ablation zone shape around a pMWA needle. MRI and MRT allowed volumetric real‐time visualization of both FHNP distribution and FHNP‐enhanced pMWA heating that was useful for intra‐procedural monitoring. This work strongly supports further development of a FHNP‐enhanced pMWA paradigm; as all individual components of this approach are approved for patient use, there is low barrier for clinical translation. [ABSTRACT FROM AUTHOR]

Transcranial magnetic stimulation (TMS) is a neurostimulation device used to modulate brain cortex activity. Our objective was to enhance the therapeutic effectiveness of low-frequency repeated TMS (LF-rTMS) in a rat model of autism spectrum disorder (ASD) induced by prenatal valproic acid (VPA) exposure through the injection of superparamagnetic iron oxide nanoparticles (SPIONs). For the induction of ASD, we administered prenatal VPA (600 mg/kg, I.P.) on the 12.5th day of pregnancy. At postnatal day 30, SPIONs were injected directly into the lateral ventricle of the brain. Subsequently, LF-rTMS treatment was applied for 14 consecutive days. Following the treatment period, behavioral analyses were conducted. At postnatal day 60, brain tissue was extracted, and both biochemical and histological analyses were performed. Our data revealed that prenatal VPA exposure led to behavioral alterations, including changes in social interactions, increased anxiety, and repetitive behavior, along with dysfunction in stress coping strategies. Additionally, we observed reduced levels of SYN, MAP2, and BDNF. These changes were accompanied by a decrease in dendritic spine density in the hippocampal CA1 area. However, LF-rTMS treatment combined with SPIONs successfully reversed these dysfunctions at the behavioral, biochemical, and histological levels, introducing a successful approach for the treatment of ASD. [ABSTRACT FROM AUTHOR]

Purpose: Lidocaine microspheres can prolong the analgesic time to 24–48 h, which still cannot meet the need of postoperative analgesia lasting more than 3 days. Therefore, we added Fe3O4 to the lidocaine microspheres and used an applied magnetic field to attract Fe3O4 to fix the microspheres around the target nerves, reducing the diffusion of magnetic lidocaine microspheres to the surrounding tissues and prolonging the analgesic time. Methods: Fe3O4–lidocaine–PLGA microspheres were prepared by the complex-emulsion volatilization method to characterize and study the release properties in vitro. The neural anchoring properties and in vivo morphology of the drug were obtained by magnetic resonance imaging. The nerve blocking effect and analgesic effect of magnetic lidocaine microspheres were evaluated by animal experiments. Results: The mean diameter of magnetically responsive lidocaine microspheres: 9.04 ± 3.23 μm. The encapsulation and drug loading of the microspheres were 46.18 ± 3.26% and 6.02 ± 1.87%, respectively. Magnetic resonance imaging showed good imaging of Fe3O4–Lidocain–PLGA microspheres, a drug-carrying model that slowed down the diffusion of the microspheres in the presence of an applied magnetic field. Animal experiments demonstrated that this preparation had a significantly prolonged nerve block, analgesic effect, and a nerve anchoring function. Conclusion: Magnetically responsive lidocaine microspheres can prolong analgesia by slowly releasing lidocaine, which can be immobilized around the nerve by a magnetic field on the body surface, avoiding premature diffusion of the microspheres to surrounding tissues and improving drug targeting. [ABSTRACT FROM AUTHOR]

Silica coated superparamagnetic Iron Oxide Nanoparticles (SPIONPS) have plenty of applications in biomedical engineering particularly drug delivery systems due to their unique efficiency and very negligible side effects. SPIONPS was synthesized rapidly using an aqueous fruit extract of Ficus carica. Single step green biosynthetic method was adapted to prepare SPIONPS in an environmentally friendly approach. The synthesized SPIONPS was subjected to different analytical studies. Results observed from UV-Visible spectroscopy and powder X-ray diffraction analysis confirms the formation of iron oxide nanoparticle. Further, the vibrating sample magnetometer confirms the paramagnetic character of the prepared sample. Particle size and scanning electron microscope analysis validate the formation of the nanoparticle. The antioxidant activity and phytochemical analysis of fruit extract and SPIONPS were analyzed to explore the presence of biomolecules, which are responsible for the reduction and stabilization of SPIONPS. In addition to the excellent superparamagnetic properties of SPIONPS are antibacterial activity against E.coli and B.stearothermophilus species. The biocompatibility of SPIONPS with the HepG-2 cell line shows its potential usefulness in drug delivery applications. [ABSTRACT FROM AUTHOR]

IntroductionThe study aimed to systematically enhance the fabrication process of flurbiprofen-loaded bilosomes (FSB) using Quality by Design (QbD) principles and Design of Experiments (DOE). The objective was to develop an optimized formulation with improved entrapment efficiency and targeted drug delivery capabilities.MethodsThe optimization process involved applying QbD principles and DOE to achieve the desired formulation characteristics. Superparamagnetic iron oxide nanoparticles (SPIONs) were incorporated to impart magnetic responsiveness. The size, entrapment efficiency, morphology, and in vitro release patterns of the FSB formulation were evaluated. Additionally, an in situ forming hydrogel incorporating FSB was developed, with its gelation time and drug release kinetics assessed. In vivo studies were conducted on osteoarthritic rats to evaluate the efficacy of the FSB-loaded hydrogel.ResultsThe optimized FSB formulation yielded particles with a size of 453.60 nm and an entrapment efficiency of 91.57%. The incorporation of SPIONs enhanced magnetic responsiveness. Morphological evaluations and in vitro release studies confirmed the structural integrity and sustained release characteristics of the FSB formulation. The in situ forming hydrogel exhibited a rapid gelation time of approximately 40 ± 1.8 s and controlled drug release kinetics. In vivo studies demonstrated a 27.83% reduction in joint inflammation and an 85% improvement in locomotor activity in osteoarthritic rats treated with FSB-loaded hydrogel.DiscussionThis comprehensive investigation highlights the potential of FSB as a promising targeted drug delivery system for the effective management of osteoarthritis. The use of QbD and DOE in the formulation process, along with the integration of SPIONs, resulted in an optimized FSB formulation with enhanced entrapment efficiency and targeted delivery capabilities. The in situ forming hydrogel further supported the formulation’s applicability for injectable applications, providing rapid gelation and sustained drug release. The in vivo results corroborate the formulation’s efficacy, underscoring its potential for improving the treatment of osteoarthritis.

Background: Obesity acts as one of most prevalent perilous health affairs. Male obesity -associated secondary hypogonadism (MOSH) is one of many of its complexities, which is mounting in parallel with the aggravation of obesity. Magnetic nanoparticles seem to be advanced favorable trend in multiple biomedical fields. Aim: In this study, we explore therapeutic effects of superparamagnetic iron oxide nanoparticles (SPIONs) coated with carboxymethyl cellulose (CMC) on an obese male rat model with MOSH syndrome, comparing their impacts with a well-known anti-obesity medication (Orlistat). Methods: 42 male albino rats splitted into 7 equal groups: 1-negative control: non-obese, untreated; 35 rats fed the high fat-high fructose (HFHF) diet for period of 12 weeks. Obese rats splitted into 6 equal groups; 2-positive control: obese untreated; 3-obese given Orlistat (30mg/kg); 4-obese given CMC-SPIONs (25mgFe/kg); 5-obese given CMC-SPIONs (50mgFe/kg); 6-obese given CMC-SPIONs(25mgFe/kg) + Orlistat(30mg/kg), 7-obese given CMC-SPIONs (50mgFe/kg) + Orlistat (30mg/kg); all treatments given orally for 4 weeks. During sacrifice, blood serum and sectioned hypothalamic, pituitary, testicular and adipose tissues were collected for biochemical and biomolecular assessments. Results: HFHF-diet for 12 weeks resulted in significant upsurge in BW, BMI, serum fasting glucose, insulin resistance, TAG, TC and LDL-c; HDL-c was dropped. Serum FSH, LH and testosterone values declined. A significant disorder in expression levels of genes regulating HPT-axis pathway. Hypothalamic GnRH, Kisspeptin-1, Kisspeptin-r1 and Adipo-R1 values declined. GnIH and Leptin-R1 values raised up. Pituitary GnRH-R values declined. Testicular tissue STAR, HSD17B3 and CYP19A1 values declined. Adipose tissue adiponectin declined, while leptin raised up. CMC-SPIONs 25mg and 50mg could modulate the deranged biochemical parameters and correct the deranged expression levels of all previous genes. Co-treatments revealed highly synergistic effects on all parameters. Overall, CMC-SPIONs have significant efficiency whether alone or with Orlisat in limiting obesity and consequence subfertility. Conclusion: CMC-SPIONs act as incoming promising contender for obesity and MOSH disorders management, and need more studies to their mechanisms. [Open Vet J 2024; 14(1.000): 428-437]

Mesenchymal stem cells (MSCs) have significant therapeutic potential and their use requires in-depth studies to better understand their effects. Labeling cells with superparamagnetic iron oxide nanoparticles allows real-time monitoring of their location, migration, and fate post-transplantation. This study aimed to investigate the efficacy and cytotoxicity of magnetic–fluorescent nanoparticles in human adipose tissue-derived mesenchymal stem cells (hADSCs). The efficacy of Molday ION rhodamine B (MIRB) labeling in hADSCs was evaluated and their biocompatibility was assessed using various techniques and differentiation assays. Prussian blue and fluorescence staining confirmed that 100% of the cells were labeled with MIRB and this labeling persisted for at least 3 days. Transmission electron microscopy revealed the internalization and clustering of the nanoparticles on the outer surface of the cell membrane. The viability assay showed increased cell viability 3 days after nanoparticle exposure. Cell counts were higher in the MIRB-treated group compared to the control group at 3 and 5 days and an increased cell proliferation rate was observed at 3 days post-exposure. Adipogenic, osteogenic, and chondrogenic differentiation was successfully achieved in all groups, with MIRB-treated cells showing an enhanced differentiation rate into adipocytes and osteocytes. MIRB was efficiently internalized by hADSCs but induced changes in cellular behavior due to the increased cell proliferation rate.

Adipose mesenchymal stem cells (ASCs) represent a promising therapeutic approach in inflammatory neurological disorders, including multiple sclerosis (MS). Recent lines of evidence indicate that most biological activities of ASCs are mediated by the delivery of soluble factors enclosed in extracellular vesicles (EVs). Indeed, we have previously demonstrated that small EVs derived from ASCs (ASC-EVs) ameliorate experimental autoimmune encephalomyelitis (EAE), a murine model of MS. The precise mechanisms and molecular/cellular target of EVs during EAE are still unknown. To investigate the homing of ASC-EVs, we intravenously injected small EVs loaded with ultra-small superparamagnetic iron oxide nanoparticles (USPIO) at disease onset in EAE-induced C57Bl/6J mice. Histochemical analysis and transmission electron microscopy were carried out 48 h after EV treatment. Moreover, to assess the cellular target of EVs, flow cytometry on cells extracted ex vivo from EAE mouse lymph nodes was performed. Histochemical and ultrastructural analysis showed the presence of labeled EVs in lymph nodes but not in lungs and spinal cord of EAE injected mice. Moreover, we identified the cellular target of EVs in EAE lymph nodes by flow cytometry: ASC-EVs were preferentially located in macrophages, with a consistent amount also noted in dendritic cells and CD4+ T lymphocytes. This represents the first direct evidence of the privileged localization of ASC-EVs in draining lymph nodes of EAE after systemic injection. These data provide prominent information on the distribution, uptake and retention of ASC-EVs, which may help in the development of EV-based therapy in MS. [ABSTRACT FROM AUTHOR]

Non-coding RNA (ncRNA)-based therapeutics that induce RNA interference (RNAi), such as microRNAs (miRNAs), have drawn considerable attention as a novel class of targeted cancer therapeutics because of their capacity to specifically target oncogenes/protooncogenes that regulate key signaling pathways involved in carcinogenesis, tumor growth and progression, metastasis, cell survival, proliferation, angiogenesis, and drug resistance. However, clinical translation of miRNA-based therapeutics, in particular, has been challenging due to the ineffective delivery of ncRNA molecules into tumors and their uptake into cancer cells. Recently, superparamagnetic iron oxide-based nanoparticles (SPIONs) have emerged as highly effective and efficient for the delivery of therapeutic RNAs to malignant tissues, as well as theranostic (therapy and diagnostic) applications, due to their excellent biocompatibility, magnetic responsiveness, broad functional surface modification, safety, and biodistribution profiles. This review highlights recent advances in the use of SPIONs for the delivery of ncRNA-based therapeutics with an emphasis on their synthesis and coating strategies. Moreover, the advantages and current limitations of SPIONs and their future perspectives are discussed. [ABSTRACT FROM AUTHOR]

In the fight against antibiotic resistance, which is rising to dangerously high levels worldwide, new strategies based on antibiotic-conjugated biocompatible polymers bound to magnetic nanoparticles that allow the drug to be manipulated and delivered to a specific target are being proposed. Here, we report the direct surface engineering of nontoxic iron oxide nanoparticles (IONs) using biocompatible dextran (Dex) covalently linked to β-cyclodextrin (β-CD) with the ability to form non-covalent complexes with silver-sulfamethazine (SMT-Ag). To achieve a good interaction of β-CD-modified dextran with the surface of the nanoparticles, it was functionalized with diphosphonic acid (DPA) that provides strong binding to Fe atoms. The synthesized polymers and nanoparticles were characterized by various methods, such as nuclear magnetic resonance (NMR), Fourier transform infrared (FTIR) and ultraviolet–visible (UV–Vis) spectroscopies, transmission electron microscopy (TEM), thermogravimetric analysis (TGA), atomic absorption spectroscopy (AAS), dynamic light scattering (DLS), etc. The resulting magnetic ION@DPA-Dex-β-CD-SMT-Ag nanoparticles were colloidally stable in water and contained 24 μg of antibiotic per mg of the particles. When tested for in vitro antimicrobial activity on Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria and fungi (yeast Candida albicans and mold Aspergillus niger), the particles showed promising potential. [ABSTRACT FROM AUTHOR]

Background: Obesity is one of the most prevalent and perilous health affairs. Male obesity-associated secondary hypogonadism (MOSH) is one of many of its complexities, which is mounting in parallel with the aggravation of obesity. Magnetic nanoparticles seem to be an advanced favorable trend in multiple biomedical fields. Aim: In this study, we explore the therapeutic effects of superparamagnetic iron oxide nanoparticles (SPIONs) coated with carboxymethyl cellulose (CMC) on an obese male rat model with MOSH syndrome, comparing their impacts with a well-known anti-obesity medication (Orlistat). Methods: 42 male albino rats split into 7 equal groups: 1-negative control: nonobese, untreated; 35 rats fed the high fat-high fructose (HFHF) diet for a period of 12 weeks. Obese rats splitted into 6 equal groups; 2-positive control: obese untreated; 3-obese given Orlistat (30 mg/kg); 4-obese given CMC-SPIONs (25 mgFe/kg); 5-obese given CMCSPIONs (50 mgFe/kg); 6-obese given CMC-SPIONs(25 mgFe/kg) + Orlistat (30 mg/kg), 7-obese given CMC-SPIONs (50 mgFe/kg) + Orlistat (30 mg/kg); all treatments given orally for 4 weeks. During sacrifice, blood serum and sectioned hypothalamic, pituitary, testicular, and adipose tissues were collected for biochemical and biomolecular assessments. Results: The HFHF diet for 12 weeks resulted in a significant upsurge in body weight, body mass index, serum fasting glucose, insulin resistance, TAG, total cholesterol, and LDL-c; HDL-c was dropped. Serum FSH, LH, and testosterone values declined. A significant disorder in expression levels of genes regulating the hypothalamic-pituitarytesticular- axis pathway. Hypothalamic GnRH, Kisspeptin-1, Kisspeptin-r1, and Adipo-R1 values declined. GnIH and Leptin-R1 values raised up. Pituitary GnRH-R values declined. Testicular tissue STAR, HSD17B3, and CYP19A1 values declined. Adipose tissue adiponectin declined, while leptin raised up. CMC-SPIONs 25–50 mg could modulate the deranged biochemical parameters and correct the deranged expression levels of all previous genes. Co-treatments revealed highly synergistic effects on all parameters. Overall, CMC-SPIONs have significant efficiency whether alone or with Orlisat in limiting obesity and consequence subfertility. Conclusion: CMC-SPIONs act as an incoming promising contender for obesity and MOSH disorders management, and need more studies on their mechanisms. [ABSTRACT FROM AUTHOR]

In this study, a high-efficiency superparamagnetic drug delivery system was developed for preclinical treatment of bladder cancer in small animals. Two types of nanoparticles with magnetic particle imaging (MPI) capability, i.e., single- and multi-core superparamagnetic iron oxide nanoparticles (SPIONs), were selected and coupled with bladder anti-tumor drugs by a covalent coupling scheme. Owing to the minimal particle size, magnetic field strengths of 270 mT with a gradient of 3.2 T/m and 260 mT with a gradient of 3.7 T/m were found to be necessary to reach an average velocity of 2 mm/s for single- and multi-core SPIONs, respectively. To achieve this, a method of constructing an in vitro magnetic field for drug delivery was developed based on hollow multi-coils arranged coaxially in close rows, and magnetic field simulation was used to study the laws of the influence of the coil structure and parameters on the magnetic field. Using this method, a magnetic drug delivery system of single-core SPIONs was developed for rabbit bladder therapy. The delivery system consisted of three coaxially and equidistantly arranged coils with an inner diameter of Φ50 mm, radial height of 85 mm, and width of 15 mm that were positioned in close proximity to each other. CCK8 experimental results showed that the three types of drug-coupled SPION killed tumor cells effectively. By adjusting the axial and radial positions of the rabbit bladder within the inner hole of the delivery coil structure, the magnetic drugs injected could undergo two-dimensional delivery motions and were delivered and aggregated to the specified target location within 12 s, with an aggregation range of about 5 mm × 5 mm. In addition, the SPION distribution before and after delivery was imaged using a home-made open-bore MPI system that could realistically reflect the physical state. This study contributes to the development of local, rapid, and precise drug delivery and the visualization of this process during cancer therapy, and further research on MPI/delivery synchronization technology is planned for the future.

Background: Quercetin (QC) possesses a variety of health-promoting effects in pure and in conjugation with nanoparticles. Since the mRNA-SIRT1/p66Shc pathway and microRNAs (miRNAs) are implicated in the oxidative process, we aimed to compare the effects of QC and QC-conjugated superparamagnetic iron oxide nanoparticles (QCSPIONs) on this pathway. Methods: Through the use of the chemical coprecipitation technique (CPT), SPIONs were synthesized, coated with dextran, and conjugated with quercetin. Adult male Wistar rats were given intraperitoneal injections of streptozotocin to look for signs of type 1 diabetes (T1D). The animals were randomized into five groups: the control group got deionized water (DI), free QC solution (25 mg/kg), SPIONs (25 mg/kg), and QCSPIONs (25 mg/kg), and all groups received repeat doses administered orally over 35 days. Real-time quantitative PCR was used to assess the levels of miR-34a, let-7a-p5, SIRT1, p66Shc, CASP3, and PARP1 expression in the hippocampus of diabetic rats. Results: In silico investigations identified p66Shc, CASP3, and PARP1 as targets of let-7a-5p and miR-34a as possible regulators of SIRT1 genes. The outcomes demonstrated that diabetes elevated miR-34a, p66Shc, CASP3, and PARP1 and downregulated let-7a-5p and SIRT1 expression. In contrast to the diabetic group, QCSPIONs boosted let-7a-5p expression levels and consequently lowered p66Shc, CASP3, and PARP1 expression levels. QCSPIONs also reduced miR-34a expression, which led to an upsurge in SIRT1 expression. Conclusion: Our results suggest that QCSPIONs can regulate the SIRT1/p66Shc-mediated signaling pathway and can be considered a promising candidate for ameliorating the complications of diabetes. [ABSTRACT FROM AUTHOR]

[Display omitted] Despite the large number of synthesis methodologies described for superparamagnetic iron oxide nanoparticles (SPIONs), the search for their large-scale production for their widespread use in biomedical applications remains a mayor challenge. Flame Spray Pyrolysis (FSP) could be the solution to solve this limitation, since it allows the fabrication of metal oxide nanoparticles with high production yield and low manufacture costs. However, to our knowledge, to date such fabrication method has not been upgraded for biomedical purposes. Herein, SPIONs have been fabricated by FSP and their surface has been treated to be subsequently coated with dimercaptosuccinic acid (DMSA) to enhance their colloidal stability in aqueous media. The final material presents high quality in terms of nanoparticle size, homogeneous size distribution, long-term colloidal stability and magnetic properties. A thorough in vitro validation has been performed with peripheral blood cells and mesenchymal stem cells (hBM-MSCs). Specifically, hemocompatibility studies show that these functionalized FSP-SPIONs-DMSA nanoparticles do not cause platelet aggregation or impair basal monocyte function. Moreover, in vitro biocompatibility assays show a dose-dependent cellular uptake while maintaining high cell viability values and cell cycle progression without causing cellular oxidative stress. Taken together, the results suggest that the FSP-SPIONs-DMSA optimized in this work could be a worthy alternative with the benefit of a large-scale production aimed at industrialization for biomedical applications. [ABSTRACT FROM AUTHOR]

Beyond their CO2 emittance when burned as fuels, hydrocarbons (HCs) serve as omnipresent raw materials and commodities. No matter if as liquid oil spills or the endless amounts of plastic roaming the oceans, HCs behave as persistent pollutants with water as main carrier to distribute. Even if their general chemical structure [‐(CH2)n‐] is quite simple, the endless range of n leads to contaminations of different appearances and properties. A water remediation method based on superparamagnetic iron oxide nanoparticles (SPIONs) modified with self‐assembled monolayers of alkyl phosphonic acid derivatives is presented. These molecules enable the SPIONs to non‐covalently bind HCs, independently from the molecular weight, size and morphology. The attractive interaction is mainly based on hydrophobic and Coulomb interaction, which allows recycling of the SPIONs. The superparamagnetic core allows a simple magnetic collection and separation from the water phase which makes it a promising addition to wastewater treatment. Agglomerates of collected plastic "waste" even exhibit superior adsorption properties for crude oil, another hydrocarbon waste which gives these collected wastes a second life. This upcycling approach combined with presented recycling methods enables a complete recycling loop. [ABSTRACT FROM AUTHOR]

Purpose: Magnetic particle imaging (MPI) is being explored in biological contexts that require accurate and reproducible quantification of superparamagnetic iron oxide nanoparticles (SPIONs). While many groups have focused on improving imager and SPION design to improve resolution and sensitivity, a few have focused on improving quantification and reproducibility of MPI. The aim of this study was to compare MPI quantification results by two different systems and the accuracy of SPION quantification performed by multiple users at two institutions. Procedures: Six users (3 from each institute) imaged a known amount of Vivotrax + (10 μg Fe), diluted in a small (10 μL) or large (500 μL) volume. These samples were imaged with or without calibration standards in the field of view, to create a total of 72 images (6 users × triplicate samples × 2 sample volumes × 2 calibration methods). These images were analyzed by the respective user with two region of interest (ROI) selection methods. Image intensities, Vivotrax + quantification, and ROI selection were compared across users, within and across institutions. Results: MPI imagers at two different institutes produce significantly different signal intensities, that differ by over 3 times for the same concentration of Vivotrax +. Overall quantification yielded measurements that were within ± 20% from ground truth; however, SPION quantification values obtained at each laboratory were significantly different. Results suggest that the use of different imagers had a stronger influence on SPION quantification compared to differences arising from user error. Lastly, calibration conducted from samples in the imaging field of view gave the same quantification results as separately imaged samples. Conclusions: This study highlights that there are many factors that contribute to the accuracy and reproducibility of MPI quantification, including variation between MPI imagers and users, despite pre-defined experimental setup, image acquisition parameters, and ROI selection analysis. [ABSTRACT FROM AUTHOR]

Superparamagnetic iron oxide nanoparticles (SPIONs) have garnered significant attention in the medical sector due to their exceptional superparamagnetic properties and reliable tracking capabilities. In this study, we investigated the immunotoxicity of SPIONs with a modified surface to enhance hydrophilicity and prevent aggregate formation. The synthesized SPIONs exhibited a remarkably small size (~4 nm) and underwent surface modification using a novel "haircut" reaction strategy. Experiments were conducted in vitro using a human monocytic cell line (THP-1). SPIONs induced dose-dependent toxicity to THP-1 cells, potentially by generating ROS and initiating the apoptotic pathway in the cells. Concentrations up to 10 μg/mL did not affect the expression of Nrf2, HO-1, NF-κB, or TLR-4 proteins. The results of the present study demonstrated that highly hydrophilic SPIONs were highly toxic to immune cells; however, they did not activate pathways of inflammation and immune response. Further investigation into the mechanisms of cytotoxicity is warranted to develop a synthetic approach for producing effective, highly hydrophilic SPIONs with little to no side effects. [ABSTRACT FROM AUTHOR]

Abstract Beyond their CO2 emittance when burned as fuels, hydrocarbons (HCs) serve as omnipresent raw materials and commodities. No matter if as liquid oil spills or the endless amounts of plastic roaming the oceans, HCs behave as persistent pollutants with water as main carrier to distribute. Even if their general chemical structure [‐(CH2)n‐] is quite simple, the endless range of n leads to contaminations of different appearances and properties. A water remediation method based on superparamagnetic iron oxide nanoparticles (SPIONs) modified with self‐assembled monolayers of alkyl phosphonic acid derivatives is presented. These molecules enable the SPIONs to non‐covalently bind HCs, independently from the molecular weight, size and morphology. The attractive interaction is mainly based on hydrophobic and Coulomb interaction, which allows recycling of the SPIONs. The superparamagnetic core allows a simple magnetic collection and separation from the water phase which makes it a promising addition to wastewater treatment. Agglomerates of collected plastic “waste” even exhibit superior adsorption properties for crude oil, another hydrocarbon waste which gives these collected wastes a second life. This upcycling approach combined with presented recycling methods enables a complete recycling loop.

Herein, a simplistic co-precipitation method was utilized to synthesize SPION@L-Tryptophan (LT)-Cu2+/Cu0 nanocomposite and probed as a novel nano-photocatalyst for the sequestration of aromatic contaminants and azo dyes. Magnetically recyclable nano-photocatalyst was characterized by X-ray diffraction (XRD), fourier transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), scanning electron microscope (SEM), transmission electron microscopy(TEM), X-ray photoelectron spectroscopy (XPS), energy dispersive X-ray analysis (EDX), Brunauer–Emmett–teller (BET), and vibrating sample magnetometer (VSM). XRD shows the presence of new peaks, which justifies the formation of SPION@LT-Cu0 nano-photocatalyst. In XPS, the peak at a binding energy of 931.93 eV shows the reduction of Cu2+ into Cu0. The catalytic efficacy of SPION@LT-Cu2+/Cu0 was thoroughly investigated for the photocatalytic reduction of nitrobenzene, 4-nitroaniline, 4-nitrophenol, methylene blue, methyl orange, and congo red in the presence of NaBH4. In addition, the synthesized nano-photocatalyst is highly efficient for the degradation of methylene blue under visible light irradiation. The results show that the synthesized nanocatalyst exhibits high catalytic efficacy and can be easily separated using an external magnetic field. Efficient catalytic activity, economic feasibility, and efficient reusability even after seven cycles ascertained that SPION@LT-Cu2+/C0 is a potential nano-photocatalyst for removing NB, 4-NA, 4-NP, MB, MO, and CR from wastewater. [ABSTRACT FROM AUTHOR]

Background: Sentinel lymph node (SLN) status is pivotal for treatment decision-making in patients with breast cancer. Superparamagnetic iron oxide nanoparticles (SPIO) have been shown to be equivalent to the dual technique with technetium99m (Tc99) and blue dye (BD) for SLN detection. The aim of this study was to determine the feasibility of detecting SLNs using an ultra-low dose of SPIO. Method: Patients planned for breast conserving surgery and SLN biopsy were included. An intradermal injection of 0.1 mL SPIO was administered at the areolar border up to 7 days before surgery. Tc99/BD was administered according to clinical routine. SLNs were detected during surgery using a handheld magnetometer. All nodes with a magnetic and/or radioactive signal, as well as blue or clinically suspicious nodes, were harvested and analyzed. Results: In 50 patients, SPIO was injected a median of 4 days before surgery. At least one SLN was found in all patients with both methods. A total of 98 SLNs were removed; 90 were detected using SPIO and 88 using Tc99/BD. Of the 90 SLNs detected by SPIO, 80 were Tc99/BD positive (concordance 89%). Histopathological analysis classified 16 patients with tumor cells deposit and 9 with macro-metastasis > 2mm, where one SLN was identified only by the radioactive technique and one only by the magnetic technique. Discussion: SLN detection using 0.1 mL ultra-low dose SPIO injected intradermally was successful in all patients. A future analysis will determine whether the approach using an ultra-low dose of SPIO injected intradermally will minimize skin staining and MRI artefacts. [ABSTRACT FROM AUTHOR]

The colloidal dispersion in a nonpolar medium is an essential material for electrophoretic displays (EPD) with low‐power consumption. A uniform‐sized superparamagnetic iron oxide nanoparticle (SPION) is a promising candidate for EPD, which exhibits tunable structural color by Bragg diffraction. In this study, the surface of SPION is charged in a nonpolar medium by inverse micelles of Solsperse‐17k, an oil‐soluble polymeric surfactant. A photonic ink of SPION dispersion exhibits simultaneous magnetochromism and electrochromism. The photonic ink is encapsulated via a complex coacervation process, in which double layers of gelatin/gum Arabic form a stable shell for µ‐capsule. The µ‐capsules show tunable structural colors, which depends upon the size of SPION in photonic ink. The increased surfactant content in photonic ink brings about a decrease in µ‐capsule size due to a reduced surface tension. A lowered gelatin concentration during coacervation results in a smaller µ‐capsule, which exhibits an electrical color tunability. Optical characterization using a confocal microscopy enables 3D visualization of the inner structure of µ‐capsules and the formation of particle chain structure of SPION in H‐field. The encapsulated photonic ink exhibits magnetochromism for 1 year, illuminating the long‐term stability of µ‐capsules developed in this study. [ABSTRACT FROM AUTHOR]

Moexitecan (Mex) is a novel camptothecin derivative that retains the potent antitumor properties of camptothecin drugs and has improved hydrophilicity to enhance biocompatibility in vitro. However, single-drug therapy still has limitations. In this study, magnetic liposomes loaded with both moexitecan and superparamagnetic iron oxide nanoparticles (SPIO) have been fabricated by a film hydration and filtration method, which is abbreviated as Mex@MLipo. By using liposomes as drug carriers, Mex can be delivered specifically to the target site, resulting in improved therapeutic efficacy and reduced toxicity. Morphology characterization results show that Mex@MLipo has a mean diameter of 180–200 nm with a round morphology. The loading efficiencies of Mex and SPIO are 65.86% and 76.86%, respectively. Cell toxicity, in vitro cell uptake, and in vivo fluorescence imaging experiments showed that Mex@MLipo was the most effective in killing HT-29 cells compared with HepG-2 and PC-3 cells, due to its ability to combine chemotherapy and induce ferroptosis, resulting in a strong anti-tumor effect. Thus, this study developed an innovative nanoscale drug delivery system that paves the way for clinical applications of moexitecan. [ABSTRACT FROM AUTHOR]

Superparamagnetic iron oxide nanoparticles (SPION) with a "non-fouling" surface represent a versatile group of biocompatible nanomaterials valuable for medical diagnostics, including oncology. In our study we present a synthesis of novel maghemite (γ-Fe2O3) nanoparticles with positive and negative overall surface charge and their coating by copolymer P(HPMA-co-HAO) prepared by RAFT (reversible addition–fragmentation chain-transfer) copolymerization of N-(2-hydroxypropyl)methacrylamide (HPMA) with N-[2-(hydroxyamino)-2-oxo-ethyl]-2-methyl-prop-2-enamide (HAO). Coating was realized via hydroxamic acid groups of the HAO comonomer units with a strong affinity to maghemite. Dynamic light scattering (DLS) demonstrated high colloidal stability of the coated particles in a wide pH range, high ionic strength, and the presence of phosphate buffer (PBS) and serum albumin (BSE). Transmission electron microscopy (TEM) images show a narrow size distribution and spheroid shape. Alternative coatings were prepared by copolymerization of HPMA with methyl 2-(2-methylprop-2-enoylamino)acetate (MMA) and further post-polymerization modification with hydroxamic acid groups, carboxylic acid and primary-amino functionalities. Nevertheless, their colloidal stability was worse in comparison with P(HPMA-co-HAO). Additionally, P(HPMA-co-HAO)-coated nanoparticles were subjected to a bio-distribution study in mice. They were cleared from the blood stream by the liver relatively slowly, and their half-life in the liver depended on their charge; nevertheless, both cationic and anionic particles revealed a much shorter metabolic clearance rate than that of commercially available ferucarbotran. [ABSTRACT FROM AUTHOR]

Labeling of mesenchymal stem cells (MSCs) with superparamagnetic iron oxide nanoparticles (SPIONs) has emerged as a potential method for magnetic resonance imaging (MRI) tracking of transplanted cells in tissue repair studies and clinical trials. Labeling of MSCs using clinically approved SPIONs (ferumoxytol) requires the use of transfection reagents or magnetic field, which largely limits their clinical application. To overcome this obstacle, we established a novel and highly effective method for magnetic labeling of MSC spheroids using ferumoxytol. Unlike conventional methods, ferumoxytol labeling was done in the formation of a mechanically tunable biomimetic hydrogel-induced MSC spheroids. Moreover, the labeled MSC spheroids exhibited strong MRI T2 signals and good biosafety. Strikingly, the encapsulated ferumoxytol was localized in the extracellular matrix (ECM) of the spheroids instead of the cytoplasm, minimizing the cytotoxicity of ferumoxytol and maintaining the viability and stemness properties of biomimetic hydrogel-induced MSC spheroids. This demonstrates the potential of this method for post-transplantation MRI tracking in the clinic.

Background and Aim: A delivery system consisting of bone marrow mesenchymal stem cells (MSCs) loaded with polyethylene glycol (PEG) coated superparamagnetic iron oxide nanoparticles (SPIONs) was constructed to treat a rat model of cisplatin (Cis)-induced nephrotoxicity with 1/10 of the common dose of anti-tumor necrosis factor-alpha (TNF-α) antibodies (infliximab). Materials and Methods: Morphology, size, crystallinity, molecular structure, and magnetic properties of uncoated and PEG-coated SPIONs were analyzed. A delivery system consisting of MSCs containing infliximab-labeled PEG-coated SPIONs (Infliximab-PEG-SPIONs-MSCs) was generated and optimized before treatment. Fifty female Wistar rats were divided into five equal groups: Group 1: Untreated control; Group 2 (Cis): Rats were administered Cis through intraperitoneal (i.p.) injection (8 mg/kg) once a week for 4 weeks; Group 3 (Infliximab): Rats were injected once with infliximab (5 mg/kg), i.p. 3 days before Cis administration; Group 4 (Cis + MSCs): Rats were injected with Cis followed by an injection of 2 × 106 MSCs into the tail vein twice at a 1-week interval; and Group 5 (Cis + Infliximab (500 μg/kg)-PEG-SPIONs-MSCs): Rats were injected with the delivery system into the tail vein twice at a 1-week interval. Besides histological examination of the kidney, the Doppler ultrasound scanner was used to scan the kidney with the Gray-color-spectral mode. Results: In vivo, intra-renal iron uptake indicates the traffic of the delivery system from venous blood to renal tissues. Cis-induced nephrotoxicity resulted in a significant increase in TNF-α and malondialdehyde (MDA) (p < 0.05), bilirubin, creatinine, and uric acid (p < 0.01) levels compared with the untreated control group. The different treatments used in this study resulted in the amelioration of some renal parameters. However, TNF-α levels significantly decreased in Cis + Infliximab and Cis + MSCs (p < 0.05) groups. The serum levels of MDA significantly decreased in Cis + Infliximab (p < 0.05), Cis + MSCs (p < 0.05), and Cis + Infliximab-PEG-SPIONs-MSCs (p < 0.01). Furthermore, the serum activities of antioxidant enzymes were significantly elevated in the Cis + MSCs and Cis + Infliximab-PEG-SPIONs-MSCs groups (p < 0.05) compared to the Cis-induced nephrotoxicity rat model. Conclusion: With the support of the constructed MSCs-SPIONs infliximab delivery system, it will be possible to track and monitor cell homing after therapeutic application. This infliximab-loading system may help overcome some challenges regarding drug delivery to the target organ, optimize therapeutics' efficacy, and reduce the dose. The outcomes of the current study provide a better understanding of the potential of combining MSCs and antibodies-linked nanoparticles for the treatment of nephrotoxicity. However, further investigation is recommended using different types of other drugs. For new approaches development, we should evaluate whether existing toxicity analysis and risk evaluation strategies are reliable and enough for the variety and complexity of nanoparticles.

(1) Background: Sentinel lymph node biopsy is important in the search for metastases, especially in patients with malignant breast disease. Our study proposed new techniques to prevent complications such as possible postoperative seroma formation, pain or hypoesthesia of the axillary cord and medial arm surface, as well as motor deficits, to avoid disabling outcomes and presents initial data from our experience with the sentinel lymph node biopsy technique. (2) Methods: We mainly used two radioactive tracer detection techniques and a new technique using a radiotracer called Sentimag-magtrace. The positive lymph node was located and removed to perform histologic analysis. In our study, we evaluate 100 patients who underwent breast cancer surgery. (3) Results: We calculated the identification rates of the different methods of sentinel lymph node detection and found that it was 88.9% using radioactive tracers vs. 89.5% using the magnetic tracer technology (Sentimag). (4) Conclusions: Thus, this technique avoids radiation exposure for both patients and health care providers, and can reduce costs and time. [ABSTRACT FROM AUTHOR]

To improve the physical stability of nanoparticle dispersions, several methods for their transformation into stable and easily dispersible dry products have been investigated thus far. Recently, electrospinning was shown to be a novel nanoparticle dispersion drying method, which addresses the crucial challenges of the current drying methods. It is a relatively simple method, but it is affected by various ambient, process, and dispersion parameters, which impact the properties of the electrospun product. The aim of this study was, thus, to investigate the influence of the most important dispersion parameter, namely the total polymer concentration, on the drying method efficiency and the properties of the electrospun product. The formulation was based on a mixture of hydrophilic polymers poloxamer 188 and polyethylene oxide in the weight ratio of 1:1, which is acceptable for potential parenteral application. We showed that the total polymer concentration of prior-drying samples is closely related to their viscosity and conductivity, also affecting the morphology of the electrospun product. However, the change in morphology of the electrospun product does not affect the efficiency of SPION reconstitution from the electrospun product. Regardless of the morphology, the electrospun product is not in powder form and is therefore safer to handle compared to powder nanoformulations. The optimal total polymer concentration in the prior-drying SPION dispersion, which enables the formation of an easily dispersible electrospun product with high SPION-loading (65% (w/w)) and fibrillar morphology, was shown to be 4.2% (w/v). [ABSTRACT FROM AUTHOR]

Stem cell injection is good for periodontal regeneration due to the capacity of stem cells to differentiate toward osteogenic direction and to regulate the production of pro‐ and anti‐inflammatory cytokines. However, injected cells are difficult to track in vivo. And there is microbiota in oral cavity, the dysbiosis of which leads to the damage and loss of periodontal tissue. Here, we demonstrated an enhanced periodontal repair was due to an altered oral microbiota. Periodontal defects were surgically prepared in rats, and periodontal ligament stem cells (PDLSCs) labeled by superparamagnetic iron oxide (SPIO) nanoparticles (PC‐SPIO) were injected, with PDLSCs and saline treatments as controls. Detected by magnetic resonance imaging (MRI) and histological staining, PC‐SPIO was major at limited areas in regenerated periodontal tissues. PC‐SPIO‐treated rats achieved better periodontal regeneration than the other two groups. Concurrently, the oral microbiota of PC‐SPIO‐treated rats was changed, presenting SPIO‐Lac as a biomarker. SPIO‐Lac assisted periodontal repair in vivo, inhibited the inflammation of macrophages induced by lipopolysaccharide (LPS) and antibacterial in vitro. Therefore, our study proved that SPIO‐labeled cells can be tracked in periodontal defect and highlighted a potential positive role of an oral microbiota in periodontal regeneration, suggesting the possibility of periodontal repair promotion by manipulating oral microbiota. [ABSTRACT FROM AUTHOR]

Oilfield scale is one of the significant problems in hydrocarbon production in the oil and gas industry. Many research groups have attempted to develop greener chemicals to meet environmental regulations. Magnetic nanoparticles are an intriguing technology due to their multiple properties, such as size effects, surface-to-volume ratio, magnetic separation, specificity, low toxicity, and the ability to control exposure and surface chemistry. In this project, we propose a new method to remove chemicals from the produced fluids by attaching the chemicals to superparamagnetic iron oxide nanoparticles (SPIONs), allowing a facile magnetic removal and reusing and recycling. In principle, the system is fully self-contained, and no chemicals or SPIONs are discharged, reducing the overall environmental footprint. We earlier reported synthesizing and using phosphonated polyetheramines (PPEAs) as environmentally friendly and potent scale inhibitors against carbonate and sulfate oilfield scales. Herein, we report the synthesis of superparamagnetic iron oxide nanoparticles (SPIONs) functionalized with biocompatible trisodium citrate (TSC) as a stabilizer agent to avoid crystal grain growth SPIONs using a coprecipitation approach. The resultant SPIONs-TSC was further functionalized with a partially linear phosphonated polyetheramine (PPEA), as green SI, via electrostatic interaction, affording highly monodisperse SPIONs-TSC-PPEA. The synthesized SPIONs-TSC-PPEA was thoroughly characterized via various spectroscopic and analytical techniques. Moreover, to validate the proof of concept of inhibition, recovering, and recycling SPIONs-based scale inhibitors, a series of static jar tests and high-pressure dynamic tube-blocking tests at 80 bar and 100 °C under oilfield conditions were conducted. The results showed that SPIONs-TSC-PPEA gave excellent inhibition performance against the gypsum scale even when recycled four times. In addition, the morphology of the gypsum scales in the absence and presence of SPIONs-TSC-PPEA was determined using scanning electron microscopy (SEM). [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma is a hard-to-treat, deadly malignancy. Traditional treatments, such as surgery, radiation and chemotherapy, unfortunately are still not able to significantly improve long-term survival. Three-dimensional (3D) cell cultures might be a platform to study new drug types in a highly reproducible, resource-saving model within a relevant pathophysiological cellular microenvironment. We used a 3D culture of human pancreatic ductal adenocarcinoma cell lines to investigate a potential new treatment approach using superparamagnetic iron oxide nanoparticles (SPIONs) as a drug delivery system for mitoxantrone (MTO), a chemotherapeutic agent. We established a PaCa DD183 cell line and generated PANC-1SMAD4 (−/−) cells by using the CRISPR-Cas9 system, differing in a prognostically relevant mutation in the TGF-β pathway. Afterwards, we formed spheroids using PaCa DD183, PANC-1 and PANC-1SMAD4 (−/−) cells, and analyzed the uptake and cytotoxic effect of free MTO and MTO-loaded SPIONs by microscopy and flow cytometry. MTO and SPION–MTO-induced cell death in all tumor spheroids in a dose-dependent manner. Interestingly, spheroids with a SMAD4 mutation showed an increased uptake of MTO and SPION–MTO, while at the same time being more resistant to the cytotoxic effects of the chemotherapeutic agents. MTO-loaded SPIONs, with their ability for magnetic drug targeting, could be a future approach for treating pancreatic ductal adenocarcinomas. [ABSTRACT FROM AUTHOR]

Superparamagnetic iron oxide nanoparticles (SPIONs) have immeasurable potentials in many fields such as nanobiotechnology and biomedical engineering because of their superparamagnetic properties and small particle size. This review introduces the methods for SPIONs synthesis, including co-precipitation, thermal decomposition, microemulsion and hydrothermal reaction, and surface modification of SPIONs with organometallic and inorganic metals, surface modification for targeted drug delivery, and the use of SPIONs as a contrast agent. In addition, this article also provides an overview of recent progress in SPIONs for the treatment of glioma, lung cancer and breast cancer. [ABSTRACT FROM AUTHOR]

Abstract The colloidal dispersion in a nonpolar medium is an essential material for electrophoretic displays (EPD) with low‐power consumption. A uniform‐sized superparamagnetic iron oxide nanoparticle (SPION) is a promising candidate for EPD, which exhibits tunable structural color by Bragg diffraction. In this study, the surface of SPION is charged in a nonpolar medium by inverse micelles of Solsperse‐17k, an oil‐soluble polymeric surfactant. A photonic ink of SPION dispersion exhibits simultaneous magnetochromism and electrochromism. The photonic ink is encapsulated via a complex coacervation process, in which double layers of gelatin/gum Arabic form a stable shell for µ‐capsule. The µ‐capsules show tunable structural colors, which depends upon the size of SPION in photonic ink. The increased surfactant content in photonic ink brings about a decrease in µ‐capsule size due to a reduced surface tension. A lowered gelatin concentration during coacervation results in a smaller µ‐capsule, which exhibits an electrical color tunability. Optical characterization using a confocal microscopy enables 3D visualization of the inner structure of µ‐capsules and the formation of particle chain structure of SPION in H‐field. The encapsulated photonic ink exhibits magnetochromism for 1 year, illuminating the long‐term stability of µ‐capsules developed in this study.

In the fight against antibiotic resistance, which is rising to dangerously high levels worldwide, new strategies based on antibiotic-conjugated biocompatible polymers bound to magnetic nanoparticles that allow the drug to be manipulated and delivered to a specific target are being proposed. Here, we report the direct surface engineering of nontoxic iron oxide nanoparticles (IONs) using biocompatible dextran (Dex) covalently linked to β-cyclodextrin (β-CD) with the ability to form non-covalent complexes with silver-sulfamethazine (SMT-Ag). To achieve a good interaction of β-CD-modified dextran with the surface of the nanoparticles, it was functionalized with diphosphonic acid (DPA) that provides strong binding to Fe atoms. The synthesized polymers and nanoparticles were characterized by various methods, such as nuclear magnetic resonance (NMR), Fourier transform infrared (FTIR) and ultraviolet–visible (UV–Vis) spectroscopies, transmission electron microscopy (TEM), thermogravimetric analysis (TGA), atomic absorption spectroscopy (AAS), dynamic light scattering (DLS), etc. The resulting magnetic ION@DPA-Dex-β-CD-SMT-Ag nanoparticles were colloidally stable in water and contained 24 μg of antibiotic per mg of the particles. When tested for in vitro antimicrobial activity on Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria and fungi (yeast Candida albicans and mold Aspergillus niger), the particles showed promising potential.

This study aims to synthesize a magnetic resonance imaging (MRI) contrast agent that can specifically target the asialoglycoprotein receptor of liver cancer cells and evaluate its ability as a targeted MRI contrast agent. Lactobionic acid (LA) and polyethylene glycol (PEG) were used to modify superparamagnetic iron oxide nanoparticles (SPION) to obtain LA-PEG-SPION. LA-PEG-SPION was uniformly spherical under the electron microscope, with regular morphology and good dispersion. The particle size of LA-PEG-SPION was about 30 ± 4.5 nm, and its surface potential was about 31 ± 1.5 mV. LA-PEG-SPION had no toxicity or low toxicity to HepG2 cells and HeLa cells, even at 400 μg/mL. The uptake of LA-PEG-SPION by HepG2 cells was higher than that of SPION, with increased blue-stained particles. The fluorescent labeling rate of HepG2 cells reached 68.8%, which was higher than that of the control group. In vitro, MRI showed that the T2-weighted signal intensity of HepG2 cells was lower than that of the control group. Conclusively, LA-PEG-SPION nanoparticles are synthesized in a simple and efficient way. They are successfully applied to the T2-weighted contrast-enhanced MRI in liver cancer in vitro, and they have the potential to be used for in vivo research and clinical studies.