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1.
Sci Rep ; 14(1): 15538, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38969729

ABSTRACT

Drug delivery is the process or method of delivering a pharmacological product to have therapeutic effects on humans or animals. The use of nanoparticles to deliver medications to cells is driving the present surge in interest in improving human health. Green nanodrug delivery methods are based on chemical processes that are acceptable for the environment or that use natural biomaterials such as plant extracts and microorganisms. In this study, zinc oxide-superparamagnetic iron oxide-silver nanocomposite was synthesized via green synthesis method using Fusarium oxysporum fungi mycelia then loaded with sorafenib drug. The synthesized nanocomposites were characterized by UV-visibile spectroscopy, FTIR, TEM and SEM techniques. Sorafenib is a cancer treatment and is also known by its brand name, Nexavar. Sorafenib is the only systemic medication available in the world to treat hepatocellular carcinoma. Sorafenib, like many other chemotherapeutics, has side effects that restrict its effectiveness, including toxicity, nausea, mucositis, hypertension, alopecia, and hand-foot skin reaction. In our study, 40 male albino rats were given a single dose of diethyl nitrosamine (DEN) 60 mg/kg b.wt., followed by carbon tetrachloride 2 ml/kg b.wt. twice a week for one month. The aim of our study is using the zinc oxide-superparamagnetic iron oxide-silver nanocomposite that was synthesized by Fusarium oxysporum fungi mycelia as nanocarrier for enhancement the sorafenib anticancer effect.


Subject(s)
Antineoplastic Agents , Carcinoma, Hepatocellular , Liver Neoplasms , Silver , Sorafenib , Zinc Oxide , Animals , Sorafenib/pharmacology , Sorafenib/chemistry , Sorafenib/administration & dosage , Zinc Oxide/chemistry , Zinc Oxide/pharmacology , Silver/chemistry , Rats , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/administration & dosage , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/pathology , Male , Liver Neoplasms/drug therapy , Liver Neoplasms/pathology , Drug Carriers/chemistry , Fusarium/drug effects , Magnetite Nanoparticles/chemistry , Nanocomposites/chemistry , Humans , Magnetic Iron Oxide Nanoparticles/chemistry
2.
Arh Hig Rada Toksikol ; 75(2): 125-136, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38963142

ABSTRACT

Recent research has raised concern about the biocompatibility of iron oxide nanoparticles (IONPs), as they have been reported to induce oxidative stress and inflammatory responses, whilst prolonged exposure to high IONP concentrations may lead to cyto-/genotoxicity. Besides, there is concern about its environmental impact. The aim of our study was to investigate the effects of IONPs on the antioxidant defence system in freshwater fish Mozambique tilapia (Oreochromis mossambicus, Peters 1852). The fish were exposed to IONP concentration of 15 mg/L over 1, 3, 4, 15, 30, and 60 days and the findings compared to a control, unexposed group. In addition, we followed up the fish for 60 days after exposure had stopped to estimate the stability of oxidative stress induced by IONPs. Exposure affected the activity of antioxidant and marker enzymes and increased the levels of hydrogen peroxide and lipid peroxidation in the gill, liver, and brain tissues of the fish. Even after 60 days of depuration, adverse effects remained, indicating long-term nanotoxicity. Moreover, IONPs accumulated in the gill, liver, and brain tissues. Our findings underscore the potential health risks posed to non-target organisms in the environment, and it is imperative to establish appropriate guidelines for safe handling and disposal of IONPs to protect the aquatic environment.


Subject(s)
Antioxidants , Oxidative Stress , Tilapia , Animals , Oxidative Stress/drug effects , Tilapia/metabolism , Magnetic Iron Oxide Nanoparticles/toxicity , Lipid Peroxidation/drug effects , Gills/drug effects , Gills/metabolism , Liver/drug effects , Liver/metabolism , Water Pollutants, Chemical/toxicity , Water Pollutants, Chemical/analysis
3.
Wei Sheng Yan Jiu ; 53(3): 435-440, 2024 May.
Article in Chinese | MEDLINE | ID: mdl-38839585

ABSTRACT

OBJECTIVE: To investigate the effects of oral exposure to iron oxide nanoparticles(Fe_2O_3NPs) on the reproductive system of male rats. METHODS: Forty male SD rats were randomly divided into control group and low, medium, high dose groups, 10 rats in each group, normal saline and 50, 100 and 200 mg/kg Fe_2O_3NPs suspension were given by gavage, respectively. The volume of gavage was 10 mL/kg for 28 days. The body weight was weighed every three days, and the body weight changes of rats were recorded. After intraperitoneal anesthesia with 10% chloral hydrate, the rats were sacrificed by cervical dislocation, and the testis and epididymis were collected. Weigh and calculate the testicular coefficient and epididymal coefficient, the pathological sections of rat testis were observed by hematoxylin-eosin staining, the number of epididymal sperm was counted under an optical microscope and the sperm deformity rate was calculated. The activities of acid phosphatase(ACP), alkaline phosphatase(AKP), lactate dehydrogenase(LDH) and γ-glutamyl transpeptidase(γ-GT), the activity of superoxide dismutase(SOD), and the contents of glutathione(GSH) and malondialdehyde(MDA) in rat testis homogenate were detected by kit method. RESULTS: Compared with control group, there was no significant difference in body weight, testicular coefficient and epididymal coefficient in each dose group. In the medium and high dose groups, the arrangement of spermatogenic epithelium was disordered and spermatogenic cells decreased. The number of sperm in high dose group was decreased, and the sperm deformity rate in medium and high dose groups was increased(P<0.01). The activity of ACP in medium and high dose groups increased(P<0.05), and the activity of γ-GT decreased(P<0.01). There was no significant change in the activity of AKP and LDH in testicular homogenate of rats in each group(P>0.05). The level of GSH in medium dose group was increased(P<0.05), and the content of MDA in medium and high dose groups was increased(P<0.01). There was no significant difference in SOD activity among the groups(P>0.05). CONCLUSION: Under the conditions of this experiment, Fe_2O_3NPs can cause damage to the structure of rat testicular tissue, reduce the number of sperm, increase the rate of sperm deformity, interfere with the activity of marker enzymes in testicular tissue and induce oxidative stress injury, which has a negative impact on the reproductive system of male rats.


Subject(s)
Rats, Sprague-Dawley , Testis , Animals , Male , Rats , Testis/drug effects , Testis/metabolism , Testis/pathology , Administration, Oral , Epididymis/drug effects , Epididymis/metabolism , Magnetic Iron Oxide Nanoparticles/toxicity , Spermatozoa/drug effects
4.
ACS Appl Mater Interfaces ; 16(24): 30860-30873, 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38860682

ABSTRACT

The incidence of breast cancer remains high worldwide and is associated with a significant risk of metastasis to the brain that can be fatal; this is due, in part, to the inability of therapeutics to cross the blood-brain barrier (BBB). Extracellular vesicles (EVs) have been found to cross the BBB and further have been used to deliver drugs to tumors. EVs from different cell types appear to have different patterns of accumulation and retention as well as the efficiency of bioactive cargo delivery to recipient cells in the body. Engineering EVs as delivery tools to treat brain metastases, therefore, will require an understanding of the timing of EV accumulation and their localization relative to metastatic sites. Magnetic particle imaging (MPI) is a sensitive and quantitative imaging method that directly detects superparamagnetic iron. Here, we demonstrate MPI as a novel tool to characterize EV biodistribution in metastatic disease after labeling EVs with superparamagnetic iron oxide (SPIO) nanoparticles. Iron-labeled EVs (FeEVs) were collected from iron-labeled parental primary 4T1 tumor cells and brain-seeking 4T1BR5 cells, followed by injection into the mice with orthotopic tumors or brain metastases. MPI quantification revealed that FeEVs were retained for longer in orthotopic mammary carcinomas compared to SPIOs. MPI signal due to iron could only be detected in brains of mice bearing brain metastases after injection of FeEVs, but not SPIOs, or FeEVs when mice did not have brain metastases. These findings indicate the potential use of EVs as a therapeutic delivery tool in primary and metastatic tumors.


Subject(s)
Brain Neoplasms , Extracellular Vesicles , Animals , Extracellular Vesicles/metabolism , Extracellular Vesicles/chemistry , Mice , Brain Neoplasms/secondary , Brain Neoplasms/metabolism , Brain Neoplasms/diagnostic imaging , Female , Cell Line, Tumor , Iron/chemistry , Iron/metabolism , Magnetic Iron Oxide Nanoparticles/chemistry , Magnetite Nanoparticles/chemistry , Brain/metabolism , Brain/diagnostic imaging , Mice, Inbred BALB C , Breast Neoplasms/pathology , Breast Neoplasms/metabolism , Breast Neoplasms/diagnostic imaging , Humans
5.
ACS Appl Mater Interfaces ; 16(25): 31997-32016, 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38869318

ABSTRACT

Personalized medicine is a new approach to modern oncology. Here, to facilitate the application of extracellular vesicles (EVs) derived from lung cancer cells as potent advanced therapy medicinal products in lung cancer, the EV membrane was functionalized with a specific ligand for targeting purposes. In this role, the most effective heptapeptide in binding to lung cancer cells (PTHTRWA) was used. The functionalization process of EV surface was performed through the C- or N-terminal end of the heptapeptide. To prove the activity of the EVs functionalized with PTHTRWA, both a model of lipid membrane mimicking normal and cancerous cell membranes as well as human adenocarcinomic alveolar basal epithelial cells (A549) and human normal bronchial epithelial cells (BEAS-2B) have been exposed to these bioconstructs. Magnetic resonance imaging (MRI) showed that the as-bioengineered PTHTRWA-EVs loaded with superparamagnetic iron oxide nanoparticle (SPIO) cargos reach the growing tumor when dosed intravenously in NUDE Balb/c mice bearing A549 cancer. Molecular dynamics (MD) in silico studies elucidated a high affinity of the synthesized peptide to the α5ß1 integrin. Preclinical safety assays did not evidence any cytotoxic or genotoxic effects of the PTHTRWA-bioengineered EVs.


Subject(s)
Extracellular Vesicles , Lung Neoplasms , Mice, Inbred BALB C , Mice, Nude , Humans , Lung Neoplasms/pathology , Lung Neoplasms/metabolism , Extracellular Vesicles/chemistry , Extracellular Vesicles/metabolism , Animals , Mice , A549 Cells , Magnetic Iron Oxide Nanoparticles/chemistry
6.
J Mater Chem B ; 12(27): 6678-6689, 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38894640

ABSTRACT

The isolation of small extracellular vesicles (sEVs), including those secreted by pathological cells, with high efficiency and purity is highly demanded for research studies and practical applications. Conventional sEV isolation methods suffer from low yield, presence of contaminants, long-term operation and high costs. Bead-assisted platforms are considered to be effective for trapping sEVs with high recovery yield and sufficient purity for further molecular profiling. In this study, magnetically responsive beads made of calcium carbonate (CaCO3) particles impregnated with iron oxide (Fe3O4) nanoparticles are fabricated using a freezing-induced loading (FIL) method. The developed magnetic beads demonstrate sufficient magnetization and can be collected by a permanent magnet, ensuring their rapid and gentle capture from an aqueous solution. The tannic acid on the surface of magnetic beads is formed by a layer-by-layer (LbL) method and is used to induce coupling of sEVs with the surface of magnetic beads. These tannic acid coated magnetic beads (TAMB) were applied to capture sEVs derived from MCF7 and HCT116 cell lines. Quantitative data derived from nanoparticle tracking analysis (NTA) and BCA methods revealed the capture efficiency and recovery yield of about 60%. High-resolution transmission electron microscopy (HRTEM) imaging of sEVs on the surface of TAMBs indicated their structural integrity. Compared with the size exclusion chromatography (SEC) method, the proposed approach demonstrated comparable efficiency in terms of recovery yield and purity, while offering a relatively short operation time. These results highlight the high potential of the TAMB approach for the enrichment of sEVs from biological fluids, such as cell culture media.


Subject(s)
Extracellular Vesicles , Tannins , Tannins/chemistry , Humans , Extracellular Vesicles/chemistry , MCF-7 Cells , Particle Size , Surface Properties , HCT116 Cells , Magnetic Iron Oxide Nanoparticles/chemistry , Magnetite Nanoparticles/chemistry , Calcium Carbonate/chemistry , Magnetic Phenomena , Polyphenols
7.
ACS Appl Mater Interfaces ; 16(24): 30755-30765, 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38847111

ABSTRACT

In recent years, enveloped micro-nanobubbles have garnered significant attention in research due to their commendable stability, biocompatibility, and other notable properties. Currently, the preparation methods of enveloped micro-nanobubbles have limitations such as complicated preparation process, large bubble size, wide distribution range, low yield, etc. There exists an urgent demand to devise a simple and efficient method for the preparation of enveloped micro-nanobubbles, ensuring both high concentration and a uniform particle size distribution. Magnetic lipid bubbles (MLBs) are a multifunctional type of enveloped micro-nanobubble combining magnetic nanoparticles with lipid-coated bubbles. In this study, MLBs are prepared simply and efficiently by a magneto internal heat bubble generation process based on the interfacial self-assembly of iron oxide nanoparticles induced by the thermogenic effect in an alternating magnetic field. The mean hydrodynamic diameter of the MLBs obtained was 384.9 ± 8.5 nm, with a polydispersity index (PDI) of 0.248 ± 0.021, a zeta potential of -30.5 ± 1.0 mV, and a concentration of (7.92 ± 0.46) × 109 bubbles/mL. Electron microscopy results show that the MLBs have a regular spherical stable core-shell structure. The superparamagnetic iron oxide nanoparticles (SPIONs) and phospholipid layers adsorbed around the spherical gas nuclei of the MLBs, leading the particles to demonstrate commendable superparamagnetic and magnetic properties. In addition, the effects of process parameters on the morphology of MLBs, including phospholipid concentration, phospholipid proportiona, current intensity, magnetothermal time, and SPION concentration, were investigated and discussed to achieve controlled preparation of MLBs. In vitro imaging results reveal that the higher the concentration of MLBs loaded with iron oxide nanoparticles, the better the in vitro ultrasound (US) imaging and magnetic resonance imaging (MRI) results. This study proves that the magneto internal heat bubble generation process is a simple and efficient technique for preparing MLBs with high concentration, regular structure, and commendable properties. These findings lay a robust foundation for the mass production and application of enveloped micro-nanobubbles, particularly in biomedical fields and other related domains.


Subject(s)
Phospholipids , Phospholipids/chemistry , Particle Size , Magnetic Iron Oxide Nanoparticles/chemistry , Magnetite Nanoparticles/chemistry , Gases/chemistry , Microbubbles , Magnetic Fields
8.
Sci Rep ; 14(1): 14157, 2024 06 19.
Article in English | MEDLINE | ID: mdl-38898126

ABSTRACT

Oxidative stress is considered one of the main challenges for in vitro maturation (IVM) and makes assisted reproductive technology (ART), including IVF and embryonic development less effective. Reducing free radicals via biocompatible nanoparticles (NPs) is one of the most promising approaches for developing IVM. We investigated the comparative effect of green and chemically synthesized iron oxide nanoparticles (IONPs) with an aqueous extract of date palm pollen (DPP) on oocyte parameters related to the IVM process. To this end, IONPs were synthesized by chemical (Ch-IONPs) and green methods (G-IONPs using DPP) and characterized. The mature oocyte quality of the Ch-IONPs and G-IONPs groups was evaluated by JC1 and Hoechst staining, Annexin V-FITC-Propidium Iodide, 2', 7'-dichlorofluorescein diacetate, and dihydroethidium staining compared to the control group. Eventually, the mature oocytes were fertilized, promoted to blastocysts (BL), and evaluated in vitro. Compared with the control and G-IONPs groups, the Ch-IONPs-treated group produced more hydrogen peroxide and oxygen radicals. Compared with the Ch-IONPs group, the fertilization rate in the G-IONPs and control groups increased significantly. Finally, the G-IONPs and control groups exhibited a significant increase in the 2PN, 2-cell, 4-cell, 8-cell, compacted morula (CM), and BL rates compared with the Ch-IONPs group. Green synthesis of IONPs can reduce the toxicity of chemical IONPs during the IVM process. It can be concluded that G-IONPs encased with DPP compounds have the potential to protect against exogenous reactive oxygen species (ROS) production in an IVM medium, which can have a crucial effect on oocyte maturation and fertilization efficiency.


Subject(s)
Embryonic Development , Fertilization in Vitro , In Vitro Oocyte Maturation Techniques , Magnetic Iron Oxide Nanoparticles , Oocytes , Oocytes/drug effects , Oocytes/metabolism , Embryonic Development/drug effects , Fertilization in Vitro/methods , Magnetic Iron Oxide Nanoparticles/chemistry , Animals , In Vitro Oocyte Maturation Techniques/methods , Female , Reactive Oxygen Species/metabolism , Green Chemistry Technology/methods , Oxidative Stress/drug effects , Mice , Ferric Compounds
9.
BMC Complement Med Ther ; 24(1): 241, 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38902620

ABSTRACT

Iron nanoparticles comprise a significant class of inorganic nanoparticles, which discover applications in various zones by prudence of their few exciting properties. This study achieved the green synthesis of iron oxide nanoparticles (IONPs) by black cumin seed (Nigella sativa) extract, which acts as a reducing and capping agent. The iron nanoparticles and black cumin extract were synthesized in three different concentrations: (01:01, 02:04,01:04). UV-visible spectroscopy, XRD, FTIR, and AFM characterized the synthesized iron oxide nanoparticles. UV-visible spectra show the maximum absorbance peak of 01:01 concentration at 380 nm. The other concentrations, such as 02:04, peaked at 400 nm and 01:04 at 680 nm, confirming the formation of iron oxide nanoparticles. AFM analysis reveals the spherical shape of iron oxide nanoparticles. The XRD spectra reveal the (fcc) cubic crystal structure of the iron oxide nanoparticles. The FTIR analysis's peaks at 457.13, 455.20, and 457.13 cm-1 depict the characteristic iron nanoparticle synthesis. The black cumin extract-mediated iron oxide nanoparticles show substantial antibacterial, antifungal, antioxidant and anti-inflammatory activity in a dose-dependent manner.


Subject(s)
Anti-Infective Agents , Anti-Inflammatory Agents , Nigella sativa , Plant Extracts , Seeds , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Seeds/chemistry , Plant Extracts/pharmacology , Plant Extracts/chemistry , Nigella sativa/chemistry , Anti-Infective Agents/pharmacology , Anti-Infective Agents/chemistry , Free Radical Scavengers/pharmacology , Free Radical Scavengers/chemistry , Magnetic Iron Oxide Nanoparticles/chemistry , Ferric Compounds/chemistry , Green Chemistry Technology
10.
Anal Chim Acta ; 1308: 342647, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38740456

ABSTRACT

BACKGROUND: Presently, glyphosate (Gly) is the most extensively used herbicide globally, Nevertheless, its excessive usage has increased its accumulation in off-target locations, and aroused concerns for food and environmental safety. Commonly used detection methods, such as high-performance liquid chromatography and gas chromatography, have limitations due to expensive instruments, complex pre-processing steps, and inadequate sensitivity. Therefore, a facile, sensitive, and reliable Gly detection method should be developed. RESULTS: A photoelectrochemical (PEC) sensor consisting of a three-dimensional polymer phenylethnylcopper/nitrogen-doped graphene aerogel (PPhECu/3DNGA) electrode coupled with Fe3O4 NPs nanozyme was constructed for sensitive detection of Gly. The microscopic 3D network of electrodes offered fast transfer routes for photo-generated electrons and a large surface area for nanozyme loading, allowing high signal output and analytical sensitivity. Furthermore, the use of peroxidase-mimicking Fe3O4 NPs instead of natural enzyme improved the stability of the sensor against ambient temperature changes. Based on the inhibitory effect of Gly on the catalytic activity Fe3O4 NPs, the protocol achieved Gly detection in the range of 5 × 10-10 to 1 × 10-4 mol L-1. Additionally, feasibility of the detection was confirmed in real agricultural matrix including tea, maize seedlings, maize seeds and soil. SIGNIFICANCE: This work achieved facile, sensitive and reliable analysis towards Gly, and it was expected to inspire the design and utilization of 3D architectures in monitoring agricultural chemicals in food and environmental matrix.


Subject(s)
Electrochemical Techniques , Electrodes , Glycine , Glyphosate , Graphite , Nitrogen , Photochemical Processes , Graphite/chemistry , Glycine/analogs & derivatives , Glycine/chemistry , Glycine/analysis , Nitrogen/chemistry , Polymers/chemistry , Copper/chemistry , Gels/chemistry , Herbicides/analysis , Limit of Detection , Magnetite Nanoparticles/chemistry , Magnetic Iron Oxide Nanoparticles/chemistry
11.
Biomed Phys Eng Express ; 10(4)2024 May 10.
Article in English | MEDLINE | ID: mdl-38692266

ABSTRACT

Magnetic nanoparticle hyperthermia (MNPH) has emerged as a promising cancer treatment that complements conventional ionizing radiation and chemotherapy. MNPH involves injecting iron-oxide nanoparticles into the tumor and exposing it to an alternating magnetic field (AMF). Iron oxide nanoparticles produce heat when exposed to radiofrequency AMF due to hysteresis loss. Minimizing the non-specific heating in human tissues caused by exposure to AMF is crucial. A pulse-width-modulated AMF has been shown to minimize eddy-current heating in superficial tissues. This project developed a control strategy based on a simplified mathematical model in MATLAB SIMULINK®to minimize eddy current heating while maintaining a therapeutic temperature in the tumor. A minimum tumor temperature of 43 [°C] is required for at least 30 [min] for effective hyperthermia, while maintaining the surrounding healthy tissues below 39 [°C]. A model predictive control (MPC) algorithm was used to reach the target temperature within approximately 100 [s]. As a constrained MPC approach, a maximum AMF amplitude of 36 [kA/m] and increment of 5 [kA/m/s] were applied. MPC utilized the AMF amplitude as an input and incorporated the open-loop response of the eddy current heating in its dynamic matrix. A conventional proportional integral (PI) controller was implemented and compared with the MPC performance. The results showed that MPC had a faster response (30 [s]) with minimal overshoot (1.4 [%]) than PI controller (115 [s] and 5.7 [%]) response. In addition, the MPC method performed better than the structured PI controller in its ability to handle constraints and changes in process parameters.


Subject(s)
Algorithms , Hyperthermia, Induced , Neoplasms , Hyperthermia, Induced/methods , Humans , Neoplasms/therapy , Magnetite Nanoparticles/therapeutic use , Magnetite Nanoparticles/chemistry , Computer Simulation , Magnetic Fields , Models, Theoretical , Temperature , Magnetic Iron Oxide Nanoparticles/chemistry , Models, Biological
12.
ACS Nano ; 18(23): 15284-15302, 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38814737

ABSTRACT

Magnetic hyperthermia holds significant therapeutic potential, yet its clinical adoption faces challenges. One obstacle is the large-scale synthesis of high-quality superparamagnetic iron oxide nanoparticles (SPIONs) required for inducing hyperthermia. Robust and scalable manufacturing would ensure control over the key quality attributes of SPIONs, and facilitate clinical translation and regulatory approval. Therefore, we implemented a risk-based pharmaceutical quality by design (QbD) approach for SPION production using flame spray pyrolysis (FSP), a scalable technique with excellent batch-to-batch consistency. A design of experiments method enabled precise size control during manufacturing. Subsequent modeling linked the SPION size (6-30 nm) and composition to intrinsic loss power (ILP), a measure of hyperthermia performance. FSP successfully fine-tuned the SPION composition with dopants (Zn, Mn, Mg), at various concentrations. Hyperthermia performance showed a strong nonlinear relationship with SPION size and composition. Moreover, the ILP demonstrated a stronger correlation to coercivity and remanence than to the saturation magnetization of SPIONs. The optimal operating space identified the midsized (15-18 nm) Mn0.25Fe2.75O4 as the most promising nanoparticle for hyperthermia. The production of these nanoparticles on a pilot scale showed the feasibility of large-scale manufacturing, and cytotoxicity investigations in multiple cell lines confirmed their biocompatibility. In vitro hyperthermia studies with Caco-2 cells revealed that Mn0.25Fe2.75O4 nanoparticles induced 80% greater cell death than undoped SPIONs. The systematic QbD approach developed here incorporates process robustness, scalability, and predictability, thus, supporting the clinical translation of high-performance SPIONs for magnetic hyperthermia.


Subject(s)
Hyperthermia, Induced , Humans , Magnetic Iron Oxide Nanoparticles/chemistry , Particle Size , Cell Survival/drug effects , Magnetite Nanoparticles/chemistry , Magnetite Nanoparticles/therapeutic use
13.
Nanoscale ; 16(25): 11802-11824, 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38809214

ABSTRACT

Recent advancements in medical imaging have brought forth various techniques such as magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography (PET), and ultrasound, each contributing to improved diagnostic capabilities. Most recently, magnetic particle imaging (MPI) has become a rapidly advancing imaging modality with profound implications for medical diagnostics and therapeutics. By directly detecting the magnetization response of magnetic tracers, MPI surpasses conventional imaging modalities in sensitivity and quantifiability, particularly in stem cell tracking applications. Herein, this comprehensive review explores the fundamental principles, instrumentation, magnetic nanoparticle tracer design, and applications of MPI, offering insights into recent advancements and future directions. Novel tracer designs, such as zinc-doped iron oxide nanoparticles (Zn-IONPs), exhibit enhanced performance, broadening MPI's utility. Spatial encoding strategies, scanning trajectories, and instrumentation innovations are elucidated, illuminating the technical underpinnings of MPI's evolution. Moreover, integrating machine learning and deep learning methods enhances MPI's image processing capabilities, paving the way for more efficient segmentation, quantification, and reconstruction. The potential of superferromagnetic iron oxide nanoparticle chains (SFMIOs) as new MPI tracers further advanced the imaging quality and expanded clinical applications, underscoring the promising future of this emerging imaging modality.


Subject(s)
Magnetite Nanoparticles , Humans , Magnetite Nanoparticles/chemistry , Magnetic Resonance Imaging/methods , Animals , Magnetic Iron Oxide Nanoparticles/chemistry , Positron-Emission Tomography , Contrast Media/chemistry
14.
ACS Appl Bio Mater ; 7(6): 3942-3952, 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38740514

ABSTRACT

Magnetic separation is a promising alternative to chromatography for enhancing the downstream processing (DSP) of monoclonal antibodies (mAbs). However, there is a lack of efficient magnetic particles for successful application. Aiming to fill this gap, we demonstrate the suitability of bare iron oxide nanoparticles (BION) with physical site-directed immobilization of an engineered Protein A affinity ligand (rSpA) as an innovative magnetic material. The rSpA ligand contains a short peptide tag that enables the direct and stable immobilization onto the uncoated BION surface without commonly required laborious particle activation. The resulting BION@rSpA have beneficial characteristics outperforming conventional Protein A-functionalized magnetic particles: a simple, fast, low-cost synthesis, a particle size in the nanometer range with a large effective specific surface area enabling large immunoglobulin G (IgG) binding capacity, and a high magnetophoretic velocity advantageous for fast processing. We further show rapid interactions of IgG with the easily accessible rSpA ligands. The binding of IgG to BION@rSpA is thereby highly selective and not impeded by impurity molecules in perfusion cell culture supernatant. Regarding the subsequent acidic IgG elution from BION@rSpA@IgG, we observed a hampering pH increase caused by the protonation of large iron oxide surfaces after concentrating the particles in 100 mM sodium acetate buffer. However, the pH can be stabilized by adding 50 mM glycine to the elution buffer, resulting in recoveries above 85% even at high particle concentrations. Our work shows that BION@rSpA enable efficient magnetic mAb separation and could help to overcome emerging bottlenecks in DSP.


Subject(s)
Immunoglobulin G , Magnetic Iron Oxide Nanoparticles , Materials Testing , Particle Size , Magnetic Iron Oxide Nanoparticles/chemistry , Ligands , Immunoglobulin G/chemistry , Immunoglobulin G/isolation & purification , Biocompatible Materials/chemistry , Antibodies, Monoclonal/chemistry , Antibodies, Monoclonal/isolation & purification , Staphylococcal Protein A/chemistry , Staphylococcal Protein A/metabolism , Surface Properties , Ferric Compounds/chemistry
15.
Nano Lett ; 24(22): 6696-6705, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38796774

ABSTRACT

Ultra-high-field (UHF) magnetic resonance imaging (MRI) stands as a pivotal cornerstone in biomedical imaging, yet the challenge of false imaging persists, constraining its full potential. Despite the development of dual-mode contrast agents improving conventional MRI, their effectiveness in UHF remains suboptimal due to the high magnetic moment, resulting in diminished T1 relaxivity and excessively enhanced T2 relaxivity. Herein, we report a DNA-mediated magnetic-dimer assembly (DMA) of iron oxide nanoparticles that harnesses UHF-tailored nanomagnetism for fault-free UHF-MRI. DMA exhibits a dually enhanced longitudinal relaxivity of 4.42 mM-1·s-1 and transverse relaxivity of 26.23 mM-1·s-1 at 9 T, demonstrating a typical T1-T2 dual-mode UHF-MRI contrast agent. Importantly, DMA leverages T1-T2 dual-modality image fusion to achieve artifact-free breast cancer visualization, effectively filtering interference from hundred-micrometer-level false-positive signals with unprecedented precision. The UHF-tailored T1-T2 dual-mode DMA contrast agents hold promise for elevating the accuracy of MR imaging in disease diagnosis.


Subject(s)
Contrast Media , DNA , Magnetic Resonance Imaging , Magnetic Resonance Imaging/methods , Contrast Media/chemistry , Humans , DNA/chemistry , Mice , Magnetic Iron Oxide Nanoparticles/chemistry , Female , Animals , Breast Neoplasms/diagnostic imaging , Magnetite Nanoparticles/chemistry , Cell Line, Tumor
16.
Mol Pharm ; 21(6): 2767-2780, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38736196

ABSTRACT

Erastin can induce ferroptosis in tumor cells as an effective small molecule inhibitor. However, its application is hampered by a lack of water solubility. This study investigated the effects of superparamagnetic iron oxide (SPIO)-erastin-polyethylene glycol (PEG) nanoparticles prepared by loading SPIO-PEG nanoparticles with erastin on ferroptosis. SPIO-erastin-PEG nanoparticles exhibited square and spherical shapes with good dispersibility. The zeta potential and hydrodynamic size of SPIO-erastin-PEG were measured as (-37.68 ± 2.706) mV and (45.75 ± 18.88) nm, respectively. On T2-weighted imaging, the nanosystem showed significant contrast enhancement compared to no-enhancement magnetic resonance imaging (MRI). SPIO-erastin-PEG induced ferroptosis by increasing reactive oxygen species and iron content and promoting the accumulation of lipid peroxides and the degradation of glutathione peroxidase 4. Pharmacokinetic experiments revealed a half-life of 1.25 ± 0.05 h for the SPIO-erastin-PEG solution in circulation. Moreover, significant antitumorigenic effects of SPIO-erastin-PEG have been demonstrated in 5-8F cells and mouse-bearing tumors. These results indicated that the synthesized SPIO-erastin-PEG nanoplatform could induce ferroptosis effects in vitro and in vivo while exhibiting favorable physical characteristics. This approach may provide a new strategy for theranostic nanoplatform for nasopharyngeal cancer.


Subject(s)
Ferroptosis , Nasopharyngeal Neoplasms , Polyethylene Glycols , Ferroptosis/drug effects , Animals , Polyethylene Glycols/chemistry , Mice , Humans , Nasopharyngeal Neoplasms/drug therapy , Cell Line, Tumor , Magnetic Resonance Imaging/methods , Reactive Oxygen Species/metabolism , Magnetic Iron Oxide Nanoparticles/chemistry , Mice, Inbred BALB C , Mice, Nude , Xenograft Model Antitumor Assays , Ferric Compounds/chemistry , Female , Piperazines
17.
ACS Appl Mater Interfaces ; 16(21): 27055-27064, 2024 May 29.
Article in English | MEDLINE | ID: mdl-38757711

ABSTRACT

A major contributing cause to breast cancer related death is metastasis. Moreover, breast cancer metastasis often shows little symptoms until a large area of the organs is occupied by metastatic cancer cells. Breast cancer multimodal imaging is attractive since it integrates advantages from several modalities, enabling more accurate cancer detection. Glycoprotein CD44 is overexpressed on most breast cancer cells and is the primary cell surface receptor for hyaluronan (HA). To facilitate breast cancer diagnosis, we report an indocyanine green (ICG) and HA conjugated iron oxide nanoparticle (NP-ICG-HA), which enabled active targeting to breast cancer by HA-CD44 interaction and detected metastasis with magnetic particle imaging (MPI) and near-infrared fluorescence imaging (NIR-FI). When evaluated in a transgenic breast cancer mouse model, NP-ICG-HA enabled the detection of multiple breast tumors in MPI and NIR-FI, providing more comprehensive images and a diagnosis of breast cancer. Furthermore, NP-ICG-HAs were evaluated in a lung metastasis model. Upon NP-ICG-HA administration, MPI showed clear signals in the lungs, indicating the tumor sites. This is the first time that HA-based NPs have enabled MPI of cancer. NP-ICG-HAs are an attractive platform for noninvasive detection of primary breast cancer and lung metastasis.


Subject(s)
Breast Neoplasms , Hyaluronic Acid , Indocyanine Green , Lung Neoplasms , Optical Imaging , Hyaluronic Acid/chemistry , Animals , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/secondary , Lung Neoplasms/pathology , Female , Mice , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/pathology , Humans , Indocyanine Green/chemistry , Hyaluronan Receptors/metabolism , Cell Line, Tumor , Magnetite Nanoparticles/chemistry , Magnetic Iron Oxide Nanoparticles/chemistry
18.
Article in English | MEDLINE | ID: mdl-38725229

ABSTRACT

Chronic inflammatory conditions are among the most prevalent diseases worldwide. Several debilitating diseases such as atherosclerosis, inflammatory bowel disease, rheumatoid arthritis, and Alzheimer's are linked to chronic inflammation. These conditions often develop into complex and fatal conditions, making early detection and treatment of chronic inflammation crucial. Current diagnostic methods show high variability and do not account for disease heterogeneity and disease-specific proinflammatory markers, often delaying the disease detection until later stages. Furthermore, existing treatment strategies, including high-dose anti-inflammatory and immunosuppressive drugs, have significant side effects and an increased risk of infections. In recent years, superparamagnetic iron oxide nanoparticles (SPIONs) have shown tremendous biomedical potential. SPIONs can function as imaging modalities for magnetic resonance imaging, and as therapeutic agents due to their magnetic hyperthermia capability. Furthermore, the surface functionalization of SPIONs allows the detection of specific disease biomarkers and targeted drug delivery. This systematic review explores the utility of SPIONs against chronic inflammatory disorders, focusing on their dual role as diagnostic and therapeutic agents. We extracted studies indexed in the Web of Science database from the last 10 years (2013-2023), and applied systematic inclusion criteria. This resulted in a final selection of 38 articles, which were analyzed for nanoparticle characteristics, targeted diseases, in vivo and in vitro models used, and the efficacy of the therapeutic or diagnostic modalities. The results revealed that ultrasmall SPIONs are excellent for imaging arterial and neuronal inflammation. Furthermore, novel therapies using SPIONs loaded with chemotherapeutic drugs show promise in the treatment of inflammatory diseases. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Diagnostic Tools > In Vivo Nanodiagnostics and Imaging.


Subject(s)
Inflammation , Magnetic Iron Oxide Nanoparticles , Humans , Animals , Inflammation/drug therapy , Inflammation/diagnosis , Magnetic Iron Oxide Nanoparticles/chemistry , Chronic Disease , Mice
19.
Aquat Toxicol ; 272: 106961, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38781688

ABSTRACT

In recent years, the intensive production of nanoparticles with a wide application has led to their transfer to the environment, including the water ecosystem. The accumulation of nanoparticles in fish, causing various pathological changes in the host, raises certain concerns. In the current study, we investigated the penetration and bioaccumulation of Fe3O4 nanoparticles, in the liver of common carp (Cyprinus carpio Linnaeus, 1758). Common carp juveniles were exposed to Fe3O4 nanoparticles at concentrations of 10 and 100 mg. After 7 days, their livers were examined by light and transmission electron microscopes. Compared to normal fish's liver, after using a small concentration (10 mg) of nanoparticles, changes were observed in erythrocytes, hepatocytes, intracellular canaliculi, and bile ducts of the liver. At a high concentration (100 mg), the intensity of changes increased significantly. The liver's capsule was damaged, and a considerable number of hepatocytes were completely destroyed. Additionally, the walls of blood vessels and biliary ductule walls was notably disturbed. It was found that the intensity of pathologies occurring in the liver, increases proportionally with higher concentrations of nanoparticles. Confirmation via electron microscopic methods revealed that Fe3O4 nanoparticles, when administered with food to common carp, enter the fish's liver through erythrocytes localized in the lumen of blood vessels. From there, they traverse through the endothelium of vessels, proceed to hepatocytes, including cytoplasmic organelles, intracellular canaliculi, biliary ductules, and eventually reach the bile ducts. Fe3O4 nanoparticles in all structural elements of fish liver was up to 20 nm. Therefore, high concentrations of nanoparticles in the environment harms the bodies of aquatic organisms, including fish. The changes identified in the liver of common carp in the present study are valuable information in assessing possible risks to other components of the aquatic ecosystem and organisms.


Subject(s)
Carps , Liver , Water Pollutants, Chemical , Animals , Carps/metabolism , Liver/metabolism , Liver/drug effects , Liver/ultrastructure , Water Pollutants, Chemical/toxicity , Microscopy, Electron, Transmission , Magnetic Iron Oxide Nanoparticles/toxicity
20.
Biosens Bioelectron ; 260: 116448, 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-38820720

ABSTRACT

Functionalized few-layer borophene (FFB) was prepared using gallnut extract and coffee waste extract as natural exfoliating and stabilizing agents in an environmentally friendly ultrasonic and high shear exfoliation. Here, a facile precipitation method was employed to grow iron oxide nanoparticles doped with cerium (Ce-FeONPs) onto the surface of FFB. This intriguing combination of materials yielded Ce-FeONPs nanoparticles that exhibited exceptional peroxidase-like activity, efficiently catalyzing the conversion of 3,3',5,5'-tetramethylbenzidine (TMB) to a blue oxidized TMB (oxTMB) in the presence of hydrogen peroxide (H2O2). Additionally, the introduction of FFB contributes a reducibility effect to the catalytic oxidation of TMB, facilitating the restoration of the oxTMB to TMB. Thus, FFB-Ce-FeONPs showcase intriguing properties encompassing both oxidative and reductive characteristics, suggesting their potential as a reagent for repeated detection of H2O2. Moreover, a colorimetric sensing system enabled the liner detection of H2O2 spanning a concentration range from 0.08 to 1 mM, with a detection limit of 0.03 mM. Noteworthily, FFB-Ce-FeONPs demonstrated sustained efficacy over ten successive recycling cycles, as indicated by consistent slopes and observable color changes. In summary, this work reports the first application of nanoenzymes in repetitive H2O2 detection. Even after ten multiple cycles, the detection limit remains virtually unaltered, underscoring the robustness and enduring effectiveness of the engineered nanomaterial. The proposed simultaneous oxidation and reduction strategies for detecting H2O2 showed a commendable capability in ten cycles of H2O2 detection, thus providing a promising approach in the field of H2O2 detection.


Subject(s)
Biosensing Techniques , Cerium , Colorimetry , Hydrogen Peroxide , Limit of Detection , Hydrogen Peroxide/chemistry , Hydrogen Peroxide/analysis , Cerium/chemistry , Biosensing Techniques/methods , Colorimetry/methods , Oxidation-Reduction , Boron Compounds/chemistry , Green Chemistry Technology , Benzidines/chemistry , Catalysis , Magnetic Iron Oxide Nanoparticles/chemistry , Ferric Compounds/chemistry
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