Fabrication of amino- and hydroxyl dual-functionalized magnetic microporous organic network for extraction of zearalenone from traditional Chinese medicine prior to the HPLC determination.

Efficient enrichment of trace zearalenone (ZEN) from the complex traditional Chinese medicine (TCM) samples is quite difficult, but of great significance for TCM quality control. Herein, we reported a novel magnetic solid phase extraction (MSPE) strategy for ZEN enrichment using the amino- and hydroxyl dual-functionalized magnetic microporous organic network (Fe3O4@MON-NH2-OH) as an advanced adsorbent combined with the high-performance liquid chromatography (HPLC) determination. Efficient extraction of ZEN was achieved via the possible hydrogen bonding, hydrophobic, and π-π interactions between Fe3O4@MON-NH2-OH and ZEN. The adsorption capacity of Fe3O4@MON-NH2-OH for ZEN was 215.0 mg g-1 at the room temperature, which was much higher than most of the reported adsorbents. Under the optimal condition, the developed Fe3O4@MON-NH2-OH-MSPE-HPLC method exhibited wide linear range (5-2500 µg L-1), low limits of detection (1.4-35 µg L-1), less adsorbent consumption (5 mg), and large enhancement factor (95) for ZEN. The proposed method was successfully applied to detect trace ZEN from 10 kinds of real TCM samples. Conclusively, this work demonstrates the Fe3O4@MON-NH2-OH can effectively extract trace ZEN from the complex TCM matrices, which may open up a new way for the application of MONs in the enrichment and extraction of trace contaminants or active constituents from the complex TCM samples.

Self-propelling bacteria-based magnetic nanoparticles (BacMags) for targeted magnetic hyperthermia therapy against hypoxic tumors.

Magnetic hyperthermia-based cancer therapy (MHCT) holds great promise as a non-invasive approach utilizing heat generated by an alternating magnetic field for effective cancer treatment. For an efficacious therapeutic response, it is crucial to deliver therapeutic agents selectively at the depth of tumors. In this study, we present a new strategy using the naturally occurring tumor-colonizing bacteria Escherichia coli (E. coli) as a carrier to deliver magnetic nanoparticles to hypoxic tumor cores for effective MHCT. Self-propelling delivery agents, "nano-bacteriomagnets" (BacMags), were developed by incorporating anisotropic magnetic nanocubes into E. coli which demonstrated significantly improved hyperthermic performance, leading to an impressive 85% cell death in pancreatic cancer. The in vivo anti-cancer response was validated in a syngeneic xenograft model with a 50% tumor inhibition rate within 20 days and a complete tumor regression within 30 days. This proof-of-concept study demonstrates the potential of utilizing anaerobic bacteria for the delivery of magnetic nanocarriers as a smart therapeutic approach for enhanced MHCT.

Pharmacokinetic Study of Ultrasmall Superparamagnetic Iron Oxide Nanoparticles HY-088 in Rats.

BACKGROUND AND OBJECTIVE: HY-088 injection is an ultrasmall superparamagnetic iron oxide nanoparticle (USPIOs) composed of iron oxide crystals coated with polyacrylic acid (PAA) on the surface. The purpose of this study was to investigate the pharmacokinetics, tissue distribution, and mass balance of HY-088 injection. METHODS: The pharmacokinetics of [55Fe]-HY-088 and [14C]-HY-088 were investigated in 48 SD rats by intravenous injection of 8.5 (low-dose group), 25.5 (medium-dose group), and 85 (high-dose group) mg/100 µCi/kg. Tissue distribution was studied by intravenous injection of 35 mg/100 µCi/kg in 48 SD rats, and its tissue distribution in vivo was obtained by ex vivo tissue assay. At the same time, [14C]-HY-088 was injected intravenously at a dose of 25.5 mg/100 µCi/kg into 16 SD rats, and its tissue distribution in vivo was studied by quantitative whole-body autoradiography. [14C]-HY-088 and [55Fe]-HY-088 were injected intravenously into 24 SD rats at a dose of 35 mg/100 µCi/kg, and their metabolism was observed. RESULTS: In the pharmacokinetic study, [55Fe]-HY-088 reached the maximum observed concentration (Cmax) at 0.08 h in the low- and medium-dose groups of SD rats. [14C]-HY-088 reached Cmax at 0.08 h in the three groups of SD rats. The area under the concentration-time curve (AUC) of [55Fe]-HY-088 and [14C]-HY-088 increased with increasing dose. In the tissue distribution study, [55Fe]-HY-088 and [14C]-HY-088 were primarily distributed in the liver, spleen, and lymph nodes of both female and male rats. In the mass balance study conducted over 57 days, the radioactive content of 55Fe from [55Fe]-HY-088 was primarily found in the carcass, accounting for 86.42 ± 4.18% in females and 95.46 ± 6.42% in males. The radioactive recovery rates of [14C]-HY-088 in the urine of female and male rats were 52.99 ± 5.48% and 60.66 ± 2.23%, respectively. CONCLUSIONS: Following single intravenous administration of [55Fe]-HY-088 and [14C]-HY-088 in SD rats, rapid absorption was observed. Both [55Fe]-HY-088 and [14C]-HY-088 were primarily distributed in the liver, spleen, and lymph nodes. During metabolism, the radioactivity of [55Fe]-HY-088 is mainly present in the carcass, whereas the 14C-labeled [14C]-HY-088 shell PAA is eliminated from the body mainly through the urine.

Magnetic Nanoparticles: A Review on Synthesis, Characterization, Functionalization, and Biomedical Applications.

Nowadays, magnetic nanoparticles (MNPs) are applied in numerous fields, especially in biomedical applications. Since biofluidic samples and biological tissues are nonmagnetic, negligible background signals can interfere with the magnetic signals from MNPs in magnetic biosensing and imaging applications. In addition, the MNPs can be remotely controlled by magnetic fields, which make it possible for magnetic separation and targeted drug delivery. Furthermore, due to the unique dynamic magnetizations of MNPs when subjected to alternating magnetic fields, MNPs are also proposed as a key tool in cancer treatment, an example is magnetic hyperthermia therapy. Due to their distinct surface chemistry, good biocompatibility, and inducible magnetic moments, the material and morphological structure design of MNPs has attracted enormous interest from a variety of scientific domains. Herein, a thorough review of the chemical synthesis strategies of MNPs, the methodologies to modify the MNPs surface for better biocompatibility, the physicochemical characterization techniques for MNPs, as well as some representative applications of MNPs in disease diagnosis and treatment are provided. Further portions of the review go into the diagnostic and therapeutic uses of composite MNPs with core/shell structures as well as a deeper analysis of MNP properties to learn about potential biomedical applications.

Sprayable tissue adhesive microparticle-magnetic nanoparticle composites for local cancer hyperthermia.

Incomplete removal of early-stage gastrointestinal cancers by endoscopic treatments often leads to recurrence induced by residual cancer cells. To completely remove or kill cancer tissues and cells and prevent recurrence, chemotherapy, radiotherapy, and hyperthermia using biomaterials with drugs or nanomaterials are usually administered following endoscopic treatments. However, there are few biomaterials that can be applied using endoscopic devices to locally kill cancer tissues and cells. We previously reported that decyl group-modified Alaska pollock gelatin-based microparticles (denoted C10MPs) can adhere to gastrointestinal tissues under wet conditions through the formation of a colloidal gel driven by hydrophobic interactions. In this study, we combined C10MPs with superparamagnetic iron oxide nanoparticles (SPIONs) to develop a sprayable heat-generating nanomaterial (denoted SP/C10MP) for local hyperthermia of gastrointestinal cancers. The rheological property, tissue adhesion strength, burst strength, and underwater stability of SP/C10MP were improved through decyl group modification and SPION addition. Moreover, SP/C10MP that adhered to gastrointestinal tissues formed a colloidal gel, which locally generated heat in response to an alternating magnetic field. SP/C10MP successfully killed cancer tissues and cells in colon cancer-bearing mouse models in vitro and in vivo. Therefore, SP/C10MP has the potential to locally kill residual cancer tissues and cells after endoscopic treatments.

The importance of cell uptake in photothermal treatments mediated by biomimetic magnetic nanoparticles.

Biomimetic magnetic nanoparticles (BMNPs) mediated by MamC have proven to be photothermal agents able to allow an optimized cytotoxicity against tumoral cells when used simultaneously as drug nanotransporters and as hyperthermia agents. However, it remains unclear whether BMNPs need to be internalized by the cells and/or if there is a threshold for internal Fe concentration for the photothermal therapy to be effective. In this study, three different situations for photothermal treatments have been simulated to disentangle the effect of BMNPs cell uptake on cell viability after photothermal treatments. Human hepatoblastoma (HepG2) cell line was treated with suspensions of BMNPs, and protocols were developed to have only intracellular BMNPs, only extracellular BMNPs or both, followed by photothermal exposure of the treated cell cultures. Our data demonstrate that: (1) Although the heating efficiency of the photothermal agent is not altered by its location (intra/extracellular), the intracellular location of BMNPs is crucial to ensure the cytotoxic effect of photothermal treatments, especially at low Fe concentration. In fact, the concentration of BMNPs needed to reach the same cytotoxic effect following upon laser irradiation of 0.2 W/cm2 is three times larger if BMNPs are located extracellularly compared to that needed if BMNPs are located intracellularly; (2) For a given location of the BMNPs, cell death increases with BMNPs (or Fe) concentration. When BMNPs are located intracellularly, there is a threshold for Fe concentration (∼ 0.5 mM at laser power intensities of 0.1 W/cm2) needed to affect cell viability following upon cell exposure to photothermia. (3) Bulk temperature rise is not the only factor accounting for cell death. Actually, temperature increases inside the cells cause more damage to cell structures and trigger cell death more efficiently than an increase in the temperature outside the cell.

Green synthesis of biocompatible Fe3O4 magnetic nanoparticles using Citrus Sinensis peels extract for their biological activities and magnetic-hyperthermia applications.

Green synthesis of nanoparticles (NPs) is eco-friendly, biocompatible, cost-effective, and highly stable. In the present study, Citrus sinensis peel extract was utilized to the fabrication of superparamagnetic iron oxide nanoparticles (SPIONs). The fabricated SPIONs were first characterized using UV-Visible spectroscopy, Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), Transmission electron microscopy (TEM), and vibrating sample magnetometer (VSM). The UV-Vis spectra analysis displayed a peak at 259 nm due to the surface plasmon resonance. The FTIR spectrum showed bands at 3306 cm-1, and 1616 cm-1 revealed the protein's involvement in the development and capping of NPs. TEM analysis indicated that green synthesized SPIONs were spherical in shape with particle size of 20-24 nm. Magnetization measurements indicate that the synthesized SPIONs exhibited superparamagnetic behavior at room temperature. The antimicrobial activity, minimum inhibitory concentration (MIC), antioxidant potential, anti-inflammatory effect, and catalytic degradation of methylene blue by SPIONs were investigated in this study. Results demonstrated that SPIONs had variable antimicrobial effect against different pathogenic multi-drug resistant bacteria. At the highest concentration (400 µg/mL), SPIONs showed inhibition zones (14.7-37.3 mm) against all the target isolates. Furthermore, the MIC of synthesized SPIONs against Staphylococcus aureus, Streptococcus mutans, Bacillus subtilis, Escherichia coli, Klebsiella pneumonia, and Candida albicans were 3, 6.5, 6.5, 12.5, 50, 25 µg/mL, respectively. SPIONs exhibited strong antioxidant, anti-inflammatory, and catalytic dye degradation activities. Interestingly, Fe3O4 SPIONs shows optimum magnetic hyperthermia (MHT) techniques under an alternating magnetic field (AMF) measured in specific absorption rate (SAR) of 164, 230, and 286 W/g at concentrations 1, 5, and 10 mg/mL, respectively. Additionally, these newly fabricated SPIONs virtually achieve significant execution under the AMF in fluid MHT and are suitable for biomedical applications.

Insight into synthesis and characterisation of Ga0.9Fe2.1O4 superparamagnetic NPs for biomedical applications.

A Ga3+-substituted spinel magnetite nanoparticles (NPs) with the formula Ga0.9Fe2.1O4 were synthesized using both the one-pot solvothermal decomposition method (TD) and the microwave-assisted heating method (MW). Stable colloidal solutions were obtained by using triethylene glycol, which served as a NPs stabilizer and as a reaction medium in both methods. A narrow size distribution of NPs, below 10 nm, was achieved through selected nucleation and growth. The composition, structure, morphology, and magnetic properties of the NPs were investigated using FTIR spectroscopy, thermal analysis (TA), X-ray diffraction (XRD), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), and magnetic measurements. NPs with the expected spinel structure were obtained in the case of the TD method, while the MW method produced, additionally, an important amount of gallium suboxide. The NPs, especially those prepared by TD, have superparamagnetic behavior with 2.02 µB/f.u. at 300 K and 3.06 µB/f.u. at 4.2 K. For the MW sample these values are 0.5 µB/f.u. and 0.6 µB/f.u. at 300 K and 4.2 K, respectively. The MW prepared sample contains a secondary phase and very small NPs which affects both the dimensional distribution and the magnetic behavior of NPs. The NPs were tested in vitro on amniotic mesenchymal stem cells. It was shown that the cellular metabolism is active in the presence of Ga0.9Fe2.1O4 NPs and preserves an active biocompatible cytoskeleton.

Emergence of magnetic nanoparticles in photothermal and ferroptotic therapies.

With their distinctive physicochemical features, nanoparticles have gained recognition as effective multifunctional tools for biomedical applications, with designs and compositions tailored for specific uses. Notably, magnetic nanoparticles stand out as first-in-class examples of multiple modalities provided by the iron-based composition. They have long been exploited as contrast agents for magnetic resonance imaging (MRI) or as anti-cancer agents generating therapeutic hyperthermia through high-frequency magnetic field application, known as magnetic hyperthermia (MHT). This review focuses on two more recent applications in oncology using iron-based nanomaterials: photothermal therapy (PTT) and ferroptosis. In PTT, the iron oxide core responds to a near-infrared (NIR) excitation and generates heat in its surrounding area, rivaling the efficiency of plasmonic gold-standard nanoparticles. This opens up the possibility of a dual MHT + PTT approach using a single nanomaterial. Moreover, the iron composition of magnetic nanoparticles can be harnessed as a chemotherapeutic asset. Degradation in the intracellular environment triggers the release of iron ions, which can stimulate the production of reactive oxygen species (ROS) and induce cancer cell death through ferroptosis. Consequently, this review emphasizes these emerging physical and chemical approaches for anti-cancer therapy facilitated by magnetic nanoparticles, combining all-in-one functionalities.

Immobilization of α-transglucosidase on silica-coated magnetic nanoparticles and its application for production of isomaltooligosaccharide from the potato peel.

In this study, the production of isomaltooligosaccharide from potato peel starch was carried out in three steps: liquefaction, saccharification, and transglucosylation. Further, cloning α-transglucosidase gene from Aspergillus niger (GH31 family), transforming into E. coli BL21 (DE3), overexpressing and purifying the resulting protein for the production of α-transglucosidase. The generated α-transglucosidase was then bound with magnetic nanoparticles, which improved reusability up to 5 cycles with more than 60% activity. All the modifications were characterized using the following methods: Fourier transform infra-red analysis, Transmission Electron Microscopy, Field Emission Scanning Electron Microscopy, Energy Dispersive X-ray spectroscopy, X-Ray Diffraction Spectroscopy, Thermogravimetric Analysis, and Dynamic Light Scattering (DLS) analysis. Further, the optimum conditions for transglucosylation were determined by RSM as follows: enzyme-to-substrate ratio 6.9 U g-1, reaction time 9 h, temperature 45 °C, and pH 5.5 with a yield of 70 g l-1 (± 2.1). MALDI-TOF-MS analysis showed DP of the IMOs in ranges of 2-10. The detailed structural characterization of isomaltooligosaccharide by GC-MS and NMR suggested the α-(1 → 4) and α-(1 → 6)-D-Glcp residues as major constituents along with minor α-(1 → 2) and α-(1 → 3) -D-Glcp residues.

N-Hydroxysuccinamide functionalized iron oxide nanoparticles conjugated with 5-flurouracil for hyperthermic therapy of malignant liver cancer cells by DNA repair disruption.

Magnetized iron oxide nanoparticles are ideal materials for biological and biomedical applications due to their biocompatibility, super paramagnetic behavior, surface capability, and chemical stability. This research article is narrating the overview of methodologies of preparation, functionalization, characterization and applications of Fe3O4 nanoparticles. Super paramagnetic nanoparticles are studied for their hyperthermia properties. The proposed mechanism behind the hyperthermia was damaging the proteins responsible for DNA repair thereby, directly accelerating the DNA damages on cancer cells by increasing the temperature in the vicinity of the cancer cells. In this study, super paramagnetic iron oxide (Fe3O4) nanoparticles (SPIONs) and anti-cancer drug, 5-fluorouracil, functionalized with N-Hydroxysuccinimide organic molecules. A specific absorption rate at 351 nm can be achieved using UV analysis. The magnetic Fe3O4 nanoparticles had a cubic crystalline structure. FE-SEM(field emission scanning Electron microscopy) with EDAX(energy dispersive X-ray analysis) analysis shows that the size of the SPION was about 30-100 nm range and the percentage of chemical compositions was higher in the order of Fe, O, C. for particle size analysis, the SPION were positively charged derived at +9.9 mV and its conductivity is measured at 0.826 mS/cm. In-vitro anti-cancerous activity analysis in Hep-G2 cells (liver cancer cells) shows that the 5-fluorouracil functionalized SPIONs have higher inhibition rate than the bare Fe3O4 nanoparticles. The Fe3O4 nanoparticles were studied for their hyperthermic abilities at two different frequencies such as 3.05 × 106 kAm-1s-1 and 4.58 × 106 kAm-1s-1.The bare Fe3O4 at low magnetic field, 10 mg was required to raise the temperature above 42°- 45 °C and at high magnetic field, 6 mg was enough to raise the same temperature. The 5-fluorouracil functionalized Fe3O4 shows that at low magnetic field, 6 mg is required to raise the hyperthermia temperature and at high magnetic field, 3 mg is required to raise the temperature above 42°- 45 °C. the rate of heating and the temperature achieved with time can be tuned with concentrations as well as magnetic component present in the Fe3O4 nanoparticles. Beyond this concentration, the rate of cell death was observed to increase. The saturation and low residual magnetization were revealed by the magnetization analysis, making them well suited for clinical applications.

Near infrared-emitting multimodal nanosystem for in vitro magnetic hyperthermia of hepatocellular carcinoma and dual imaging of in vivo liver fibrosis.

Prolonged usage of traditional nanomaterials in the biological field has posed several short- and long-term toxicity issues. Over the past few years, smart nanomaterials (SNs) with controlled physical, chemical, and biological features have been synthesized in an effort to allay these challenges. The current study seeks to develop theranostic SNs based on iron oxide to enable simultaneous magnetic hyperthermia and magnetic resonance imaging (MRI), for chronic liver damage like liver fibrosis which is a major risk factor for hepatocellular carcinoma. To accomplish this, superparamagnetic iron oxide nanoparticles (SPIONs) were prepared, coated with a biocompatible and naturally occurring polysaccharide, alginate. The resultant material, ASPIONs were evaluated in terms of physicochemical, magnetic and biological properties. A hydrodynamic diameter of 40 nm and a transverse proton relaxation rate of 117.84 mM-1 s-1 pronounces the use of ASPIONs as an efficient MRI contrast agent. In the presence of alternating current of 300 A, ASPIONs could elevate the temperature to 45 °C or more, with the possibility of hyperthermia based therapeutic approach. Magnetic therapeutic and imaging potential of ASPIONs were further evaluated respectively in vitro and in vivo in HepG2 carcinoma cells and animal models of liver fibrosis, respectively. Finally, to introduce dual imaging capability along with magnetic properties, ASPIONs were conjugated with near infrared (NIR) dye Atto 700 and evaluated its optical imaging efficiency in animal model of liver fibrosis. Histological analysis further confirmed the liver targeting efficacy of the developed SNs for Magnetic theranostics and optical imaging as well as proved its short-term safety, in vivo.

Cell-Membrane-Coated and Cell-Penetrating Peptide-Conjugated Trimagnetic Nanoparticles for Targeted Magnetic Hyperthermia of Prostate Cancer Cells.

Prostate malignancy represents the second leading cause of cancer-specific death among the male population worldwide. Herein, enhanced intracellular magnetic fluid hyperthermia is applied in vitro to treat prostate cancer (PCa) cells with minimum invasiveness and toxicity and highly specific targeting. We designed and optimized novel shape-anisotropic magnetic core-shell-shell nanoparticles (i.e., trimagnetic nanoparticles - TMNPs) with significant magnetothermal conversion following an exchange coupling effect to an external alternating magnetic field (AMF). The functional properties of the best candidate in terms of heating efficiency (i.e., Fe3O4@Mn0.5Zn0.5Fe2O4@CoFe2O4) were exploited following surface decoration with PCa cell membranes (CM) and/or LN1 cell-penetrating peptide (CPP). We demonstrated that the combination of biomimetic dual CM-CPP targeting and AMF responsiveness significantly induces caspase 9-mediated apoptosis of PCa cells. Furthermore, a downregulation of the cell cycle progression markers and a decrease of the migration rate in surviving cells were observed in response to the TMNP-assisted magnetic hyperthermia, suggesting a reduction in cancer cell aggressiveness.

Biocompatibility of magnetic nanoparticles synthesized through green routed with a focus on hematological and histological analysis.

The interaction of metal nanoparticles (MNPs) with blood cells and tissues is essential from the perspectives of biocompatibility and the production of novel drug delivery systems. In the present study, biosynthesized-Fe3O4 nanoparticles (bio-Fe3O4 NPs) were prepared and bio-modified using Daphne mucronata Royle leaf extracts. The physicochemical properties of bio-Fe3O4 NPs were determined using UV-Visible spectroscopy, Energy-dispersive X-ray spectroscopy (EDX), X-ray powder diffraction (XRD), dynamic light scattering (DLS), and Fourier transform infrared (FT-IR) analyses. According to the SEM analysis, the bio-Fe3O4 NPs are spherical-shaped with a size range of 10-30 nm. Antibacterial effects of bio-Fe3O4 NPs against Staphylococcus aureus ATCC 43300 and Pseudomonas aeruginosa ATCC 27853 bacteria were measured by minimum inhibition/bactericidal concentrations (MIC and MBC tests). Result showed that the bio-Fe3O4 NPs (300 ppm) revealed highest antibacterial effect on S. aureus ATCC 43300. Also, bio-Fe3O4 NPs have different cell viability in the human breast cancer cell line (MCF-7) and mouse embryonic fibroblast (MEF). The interaction of bio-Fe3O4 NPs with blood cells and the complete blood count (CBC) factor illustrated that the morphology of blood cells and platelet clumping did not influence by nanoparticles. Furthermore, histological analysis of the liver, spleen, and kidney did not show any abnormality upon exposure to 100 mg kg-1 bio-Fe3O4 NPs treated samples. Hence, the biosynthesized Fe3O4 NPs are a good candidate for applications in medical fields.

Influence of the modifiers in polyol method on magnetically induced hyperthermia and biocompatibility of ultrafine magnetite nanoparticles.

Magnetite nanoparticles (Fe3O4 NPs) are widely tested in various biomedical applications, including magnetically induced hyperthermia. In this study, the influence of the modifiers, i.e., urotropine, polyethylene glycol, and NH4HCO3, on the size, morphology, magnetically induced hyperthermia effect, and biocompatibility were tested for Fe3O4 NPs synthesized by polyol method. The nanoparticles were characterized by a spherical shape and similar size of around 10 nm. At the same time, their surface is functionalized by triethylene glycol or polyethylene glycol, depending on the modifiers. The Fe3O4 NPs synthesized in the presence of urotropine had the highest colloidal stability related to the high positive value of zeta potential (26.03 ± 0.55 mV) but were characterized by the lowest specific absorption rate (SAR) and intrinsic loss power (ILP). The highest potential in the hyperthermia applications have NPs synthesized using NH4HCO3, for which SAR and ILP were equal to 69.6 ± 5.2 W/g and 0.613 ± 0.051 nHm2/kg, respectively. Their application possibility was confirmed for a wide range of magnetic fields and by cytotoxicity tests. The absence of differences in toxicity to dermal fibroblasts between all studied NPs was confirmed. Additionally, no significant changes in the ultrastructure of fibroblast cells were observed apart from the gradual increase in the number of autophagous structures.

Facile and selective separation of anthraquinones by alizarin-modified iron oxide magnetic nanoparticles.

Anthraquinones are widely distributed in higher plants and possess broad biological activities. The conventional separation procedures for isolating anthraquinones from the plant crude extracts require multiple extraction, concentration, and column chromatography steps. In this study, we synthesized three alizarin (AZ)-modified Fe3O4 nanoparticles (Fe3O4@AZ, Fe3O4@SiO2-AZ, and Fe3O4@SiO2-PEI-AZ) by thermal solubilization method. Fe3O4@SiO2-PEI-AZ showed strong magnetic responsiveness, high methanol/water dispersion, good recyclability, and high loading capacity for anthraquinones. To evaluate the feasibility of using Fe3O4@SiO2-PEI-AZ for separating various aromatic compounds, we employed molecular dynamics simulations to predict the adsorption/desorption effects of PEI-AZ for various aromatic compounds in different methanol concentrations. The results showed that the anthraquinones could be efficiently separated from the monocyclic and bicyclic aromatic compounds by adjusting the methanol/water ratio. The Fe3O4@SiO2-PEI-AZ nanoparticles were then used to separate the anthraquinones from the rhubarb extract. At 5% methanol, all the anthraquinones were adsorbed by the nanoparticles, thus allowing their separation from other components in the crude extract. Compared with the conventional separation methods, this adsorption method has the advantages of high adsorption specificity, simple operation, and solvent saving. This method sheds light on the future application of functionalized Fe3O4 magnetic nanoparticles to selectively separate desired components from complex plant and microbial crude extracts.

Fabrication of a Magnetic Porous Organic Polymer for α-Glucosidase Immobilization and Its Application in Inhibitor Screening.

The technology based on immobilized enzymes was employed to screen the constituents inhibiting disease-related enzyme activity from traditional Chinese medicine, which is expected to become an important approach of innovative drug development. Herein, the Fe3O4@POP composite with a core-shell structure was constructed for the first time with Fe3O4 magnetic nanoparticles as the core, 1,3,5-tris (4-aminophenyl) benzene (TAPB) and 2,5-divinylterephthalaldehyde (DVA) as organic monomers, and used as the support for immobilizing α-glucosidase. Fe3O4@POP was characterized by transmission electron microscopy, energy-dispersive spectrometry, Fourier transform infrared, powder X-ray diffraction, X-ray photoelectron spectroscopy, and vibrating sample magnetometry. Fe3O4@POP exhibited a distinct core-shell structure and excellent magnetic response (45.2 emu g-1). α-Glucosidase was covalently immobilized on core-shell Fe3O4@POP magnetic nanoparticles using glutaraldehyde as the cross-linking agent. The immobilized α-glucosidase possessed improved pH stability and thermal stability as well as good storage stability and reusability. More importantly, the immobilized enzyme exhibited a lower Km value and enhanced affinity for the substrate than the free one. The immobilized α-glucosidase was subsequently used for inhibitor screening from 18 traditional Chinese medicines in combination with capillary electrophoresis analysis among which Rhodiola rosea exhibited the highest enzyme inhibitory activity. These positive results demonstrated that such magnetic POP-based core-shell nanoparticles were a promising carrier for enzyme immobilization and the screening strategy based on immobilized enzyme provided an effective way to rapidly explore the targeted active compounds from medicinal plants.

Optimization of cobalt ferrite magnetic nanoparticle as a theranostic agent: MRI and hyperthermia.

OBJECTIVE: Magnetic nanoparticles (MNPs) are considered a theranostic agent in MR imaging, playing an effective role in inducing magnetic hyperthermia. Since, high-performance magnetic theranostic agents are characterized by superparamagnetic behavior and high anisotropy, in this study, cobalt ferrite MNPs were optimized and investigated as a theranostic agent. METHODS: CoFe2O4@Au@dextran particles were synthesized and characterized by DLS, HRTEM, SEM, XRD, FTIR, and VSM methods. After cytotoxicity evaluation, MR imaging parameters (r1, r2 and r2 / r1) were calculated for these nanostructures. Afterward, magnetic hyperthermia at the frequency of 425 kHz was applied to calculate specific loss power (SLP). RESULTS: Formation of CoFe2O4@Au@dextran was confirmed by UV-Visible spectrophotometry. On the basis of the relaxometric and hyperthermia induction findings of nanostructures in all stages of synthesis, the CoFe2O4@Au@dextran could produce the highest parameters of r2 and r2/r1 and SLP with values ​​of 389.7, 51.2 mM-1 s-1, and 2449 W/g, respectively. CONCLUSION: The formation of multi-core MNPs by dextran coating is expected to improve the magnetic properties of the nanostructure, leading to optimization of theranostic parameters, so that CoFe2O4@Au@dextran NPs can create contrast-enhanced images more than three times the clinical use and require less contrast agent, reducing side effects. Accordingly, CoFe2O4@Au@dextran can be introduced as a suitable theranostic nanostructure with optimal efficiency.

Controlled intracellular aggregation of magnetic particles improves permeation and retention for magnetic hyperthermia promotion and immune activation.

Rationale: Magnetic nanoparticles (MNPs) are the most used inorganic nanoparticles in clinics with therapeutic and imaging functions, but the inefficient magneto-thermal conversion efficiency, fast leakage, and uneven distribution impair their imaging sensitivity and therapeutic efficacy in tumors. Methods: Herein, we rationally designed a system containing pH-controllable charge-reversible MNPs (M20@DPA/HA) and negatively charged MMPs with different sizes (M5 and M20), which could induce intracellular aggregation. The dynamic hydrazone bonds with pH controllability were formed by the surface hydrazides on MNPs and aldehydes of hyaluronic acid (HA). Under the acidic pH, intracellular aggregation of the complex composed by M20@DPA/HA and M5 (M5&20), or M20@DPA/HA and M20 (M20&20) were investigated. In addition, the magnetic hyperthermia therapy (MHT) efficiency of tumor cells, tumor-associated macrophages polarization, giant cells formation and immune activation of tumor microenvironment were explored via a series of cell and animal model experiments. Results: Through physical and chemical characterization, the aggregation system (M20&20) exhibited a remarkable 20-fold increase in magnetothermal conversion efficiency compared to individual MNPs, together with enhanced penetration and retention inside the tumor tissues. In addition, it could promote immune activation, including repolarization of tumor-associated macrophages, as well as the formation of giant cells for T cell recruitment. As a result, the M20&20 aggregation system achieved a high degree of inhibition in 4T1 mouse mammary tumor model, with little tumor growth and metastasis after magnetic hyperthermia therapy. Conclusions: A controlled intracellular aggregation system was herein developed, which displayed an aggregation behavior under the acidic tumor microenvironment. The system significantly enhanced MHT effect on tumor cells as well as induced M1 polarization and multinucleated giant cells (MGC) formation of TAM for immune activation. This controlled aggregation system achieved barely tumor growth and metastasis, showing a promising strategy to improve MNPs based MHT on deteriorate cancers.

Bioinspired Synthesis of Magnetic Nanoparticles Based on Iron Oxides Using Orange Waste and Their Application as Photo-Activated Antibacterial Agents.

Magnetic nanoparticles based on iron oxides (MNPs-Fe) have been proposed as photothermal agents (PTAs) within antibacterial photothermal therapy (PTT), aiming to counteract the vast health problem of multidrug-resistant bacterial infections. We present a quick and easy green synthesis (GS) to prepare MNPs-Fe harnessing waste. Orange peel extract (organic compounds) was used as a reducing, capping, and stabilizing agent in the GS, which employed microwave (MW) irradiation to reduce the synthesis time. The produced weight, physical-chemical features and magnetic features of the MNPs-Fe were studied. Moreover, their cytotoxicity was assessed in animal cell line ATCC RAW 264.7, as well as their antibacterial activity against Staphylococcus aureus and Escherichia coli. We found that the 50GS-MNPs-Fe sample (prepared by GS, with 50% v/v of NH4OH and 50% v/v of orange peel extract) had an excellent mass yield. Its particle size was ~50 nm with the presence of an organic coating (terpenes or aldehydes). We believe that this coating improved the cell viability in extended periods (8 days) of cell culture with concentrations lower than 250 µg·mL-1, with respect to the MNPs-Fe obtained by CO and single MW, but it did not influence the antibacterial effect. The bacteria inhibition was attributed to the plasmonic of 50GS-MNPs-Fe (photothermal effect) by irradiation with red light (630 nm, 65.5 mW·cm-2, 30 min). We highlight the superparamagnetism of the 50GS-MNPs-Fe over 60 K in a broader temperature range than the MNPs-Fe obtained by CO (160.09 K) and MW (211.1 K). Therefore, 50GS-MNPs-Fe could be excellent candidates as broad-spectrum PTAs in antibacterial PTT. Furthermore, they might be employed in magnetic hyperthermia, magnetic resonance imaging, oncological treatments, and so on.