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Recent research has shown that etoposide (ETP), an immunomodulatory medication, can have cytotoxic effects. When accompanied by nano-drug delivery, this possibility can lead to a more effective treatment for cancer. This study involved the delivery of ETP via PDA@SPIONs (termed as ETP-PDA@SPIONs), which are superparamagnetic iron oxide nanoparticles (SPIONs) that have been coated with polydopamine (PDA) and utilized to treat C6 and U87 glioma cancer cell lines. The particle diameter, polydispersive index (PDI), zeta potential, and shape of nanoparticles were determined. The fabricated nanoparticles had a mean particle size of 164 ± 7 nm and a − 37 ± 3 mv zeta potential. Cell lines were tested for sensitivity to PDA@SPIONs, free-ETP, and ETP-PDA@SPIONs. On the cell lines, we tested the proliferation of PDA@SPIONs, free-ETP, and PDA@SPIONs loaded with ETP. The cytotoxicity of ETP-PDA@SPIONs was substantially higher than that of free-ETP-treated cells. The cells' morphological changes were examined by dual staining (acridine orange/ethidium bromide, AO/EB) and nuclear staining methods. Interestingly, this inhibitory impact was not ascribed to the known cellular membrane destruction, cell membrane damage, and reactive oxygen species (ROS). Further tests demonstrated that the nanoparticles substantially impacted mitochondrial functioning, resulting in an aberrant mitochondrial shape, and reduced mitochondrial membrane potential (MMP). Future studies into glioma cancer therapy may want to investigate using the proposed ETP-loaded nanoparticles. [Display omitted] • We establish that Etoposide with polydopamine coated superparamagnetic iron oxide nanoparticles. • The particle diameter, polydispersive index, zeta potential, and shape of nanoparticles were determined. • C6 and U87 glioma cells were tested cytotoxicity by MTT assay. • The cells' morphological changes were examined by acridine orange/ethidium bromide and nuclear staining. • Nanoparticles were induced apoptosis in mitocandrial membrane potential and reactive oxygen species pathway. [ABSTRACT FROM AUTHOR]

Circulating tumor clusters (CTC) disseminating from the primary tumor are responsible for secondary tumor formation where the conventional treatments such as chemotherapy and radiotherapy does not prevent the metastasis at locally advanced stage of breast cancer. In this study, a smart nanotheranostic system has been developed to track and eliminate the CTCs before it can colonize at a new site, which would reduce metastatic progression and increase the five-year survival rate of the breast cancer patients. Targeted multiresponsive (magnetic hyperthermia and pH) nanomicelles incorporated with NIR fluorescent superparamagnetic iron oxide nanoparticles were developed based on self-assembly for dual modal imaging and dual toxicity for spontaneous killing of CTCs in blood stream. A heterogenous tumor clusters model was developed to mimic the CTCs isolated from breast cancer patients. The nanotheranostic system was further evaluated for the targeting property, drug release kinetics, hyperthermia and cytotoxicity against developed CTC model in vitro. In vivo model in BALB/c mice equivalent to stage III and IV human metastatic breast cancer was developed to evaluate the biodistribution and therapeutic efficacy of micellar nanotheranostic system. Reduced CTCs in blood stream and low distant organ metastasis after treatment with the nanotheranostic system demonstrates its potential to capture and kill the CTCs that minimize the secondary tumor formation at distant sites. Targeted elimination of CD44 expressing circulating tumor clusters (CTC) using smart nanotheranostics prevented secondary colonization and tumor progression in immunocompetent CTC model in mice. [Display omitted] [ABSTRACT FROM AUTHOR]

The rising prevalence of bone injuries has increased the demand for minimally invasive treatments. Microbead hydrogels, renowned for cell encapsulation, provide a versatile substrate for bone tissue regeneration. They deliver bioactive agents, support cell growth, and promote osteogenesis, aiding bone repair and regeneration. In this study, we synthesized superparamagnetic iron oxide nanoparticles (Sp) coated with a calcium phosphate layer (m-Sp), achieving a distinctive flower-like micro-cluster morphology. Subsequently, sodium alginate (SA) microbead hydrogels containing m-Sp (McSa@m-Sp) were fabricated using a dropping gelation strategy. McSa@m-Sp is magnetically targetable, enhance cross-linking, control degradation rates, and provide strong antibacterial activity. Encapsulation studies with MC3T3-E1 cells revealed enhanced viability and proliferation. These studies also indicated significantly elevated alkaline phosphatase (ALP) activity and mineralization in MC3T3-E1 cells, as confirmed by Alizarin Red S (ARS) and Von Kossa staining, along with increased collagen production within the McSa@m-Sp microbead hydrogels. Immunocytochemistry (ICC) and gene expression studies supported the osteoinductive potential of McSa@m-Sp, showing increased expression of osteogenic markers including RUNX-2, collagen-I, osteopontin, and osteocalcin. Thus, McSa@m-Sp microbead hydrogels offer a promising strategy for multifunctional scaffolds in bone tissue engineering. [ABSTRACT FROM AUTHOR]

Biohybrid tissue-engineered vascular grafts (TEVGs) promise long-term durability due to their ability to adapt to hosts' needs. However, the latter calls for sensitive non-invasive imaging approaches to longitudinally monitor their functionality, integrity, and positioning. Here, we present an imaging approach comprising the labeling of non-degradable and degradable TEVGs' components for their in vitro and in vivo monitoring by hybrid 1H/19F MRI. TEVGs (inner diameter 1.5 mm) consisted of biodegradable poly(lactic- co -glycolic acid) (PLGA) fibers passively incorporating superparamagnetic iron oxide nanoparticles (SPIONs), non-degradable polyvinylidene fluoride scaffolds labeled with highly fluorinated thermoplastic polyurethane (19F-TPU) fibers, a smooth muscle cells containing fibrin blend, and endothelial cells. 1H/19F MRI of TEVGs in bioreactors, and after subcutaneous and infrarenal implantation in rats, revealed that PLGA degradation could be faithfully monitored by the decreasing SPIONs signal. The 19F signal of 19F-TPU remained constant over weeks. PLGA degradation was compensated by cells' collagen and α-smooth-muscle-actin deposition. Interestingly, only TEVGs implanted on the abdominal aorta contained elastin. XTT and histology proved that our imaging markers did not influence extracellular matrix deposition and host immune reaction. This concept of non-invasive longitudinal assessment of cardiovascular implants using 1H/19F MRI might be applicable to various biohybrid tissue-engineered implants, facilitating their clinical translation. [Display omitted] [ABSTRACT FROM AUTHOR]

The transplantation of endothelial progenitor cells (EPCs) has been shown to reduce neointimal hyperplasia following arterial injury. However, the efficacy of this approach is hampered by limited homing of EPCs to the injury site. Additionally, the in vivo recruitment and metabolic activity of transplanted EPCs have not been continuously monitored. EPCs were labeled with indocyanine green (ICG)-conjugated superparamagnetic iron oxide nanoparticles (SPIONs) and subjected to external magnetic field targeting to enhance their delivery to a carotid balloon injury (BI) model in Sprague–Dawley rats. Magnetic particle imaging (MPI)/ fluorescence imaging (FLI) multimodal in vivo imaging, 3D MPI/CT imaging and MPI/FLI ex vivo imaging was performed after injury. Carotid arteries were collected and analyzed for pathology and immunofluorescence staining. The paracrine effects were analyzed by enzyme-linked immunosorbent assay. The application of a magnetic field significantly enhanced the localization and retention of SPIONs@PEG-ICG-EPCs at the site of arterial injury, as evidenced by both in vivo continuous monitoring and ex vivo by observation. This targeted delivery approach effectively inhibited neointimal hyperplasia and increased the presence of CD31-positive cells at the injury site. Moreover, serum levels of SDF-1α, VEGF, IGF-1, and TGF-β1 were significantly elevated, indicating enhanced paracrine activity. Our findings demonstrate that external magnetic field-directed delivery of SPIONs@PEG-ICG-EPCs to areas of arterial injury can significantly enhance their therapeutic efficacy. This enhancement is likely mediated through increased paracrine signaling. These results underscore the potential of magnetically guided SPIONs@PEG-ICG-EPCs delivery as a promising strategy for treating arterial injuries. [Display omitted] • External magnetic fields guided SPIONs@PEG-ICG-EPCs to damaged arteries. • Transplantation of SPIONs@PEG-ICG-EPCs reduced neointimal hyperplasia. • EPCs show potential in reducing neointimal hyperplasia following vascular injury. [ABSTRACT FROM AUTHOR]

Fine-tuning of the scaffolds structural features for bone tissue engineering can be an efficient approach to regulate the specific response of the osteoblasts. Here, we loaded magnetic nanoparticles aka superparamagnetic iron oxide nanoparticles (SPIONs) into 3D composite scaffolds based on biological macromolecules (chitosan, collagen, hyaluronic acid) and calcium phosphates for potential applications in bone regeneration, using a biomimetic approach. We assessed the effects of organic (chitosan/collagen/hyaluronic acid) and inorganic (calcium phosphates, SPIONs) phase over the final features of the magnetic scaffolds (MS). Mechanical properties, magnetic susceptibility and biological fluids retention are strongly dependent on the final composition of MS and within the recommended range for application in bone regeneration. The MS architecture/pore size can be made bespoken through changes of the final organic/inorganic ratio. The scaffolds undertake mild degradation as the presence of inorganic components hinders the enzyme catalytic activity. In vitro studies indicated that osteoblasts (SaOS-2) on MS9 had similar cell behaviour activity in comparison with the TCP control. In vivo data showed an evident development of integration and resorption of the MS composites with low inflammation activity. Current findings suggest that the combination of SPIONs into 3D composite scaffolds can be a promising toolkit for bone regeneration. [ABSTRACT FROM AUTHOR]

Proteases with highly specific activities have numerous applications, including the cleavage of affinity tags (Flag; HA; His6X) and solubility promoting partners (GST; MBP) within the context of protein isolation and purification schemes. However, commercially sourced proteases such as Tobacco Etch Virus protease (TEVp) and Human Rhinovirus (HRV) 3C protease are typically applied as single use aliquots, which limits their cost-effectiveness. In addition, the presence of residual proteases in downstream applications can complicate analysis of the protein of interest. Thus, the creation of immobilized, reusable site-specific proteases would be of significant value to the life science community. In this work, we explore two strategies for the immobilization of TEV protease onto superparamagnetic iron oxide nanoparticles (SPIONs). In one strategy, a MBP-TEVp-Streptavidin fusion protein is immobilized on biotin-functionalized SPIONs. In a second strategy, TEV protease is covalently coupled onto SPIONs directly, via amine-mediated attachment, and indirectly, via HALO-tag mediated attachment. We demonstrate activity of our immobilized proteases in the presence of a MBP-GFP fusion protein containing the TEV protease target sequence (ENLYFQ|S). We then analyze time-dependent activity, longevity, and reuse of these immobilized protein preparations, comparing each approach. The protease immobilization strategies described in this work may be useful tools for simplifying challenging protein purification protocols, in addition to providing general methods for enzyme immobilization on SPIONs. [ABSTRACT FROM AUTHOR]

• Fe 3 O 4 @SiO 2 was done at low irradiation power by Stöber and Sonochemical synthesis. • Magnetization was modified as function of shell thickness from TEOS concentration. • SiO 2 layer induces slopes and sharp bend in magnetization due to surface disorder. Magnetite nanoparticles (Fe 3 O 4 NPs) coated with silicon dioxide (SiO 2) defined as Fe 3 O 4 @SiO 2 core-shells are a viable option for the development of addressable and multifunctional nanotargets; because of their superparamagnetic properties, molecular/biological anchor and biocompatibility in nanomedicine and theragnostics. In this work, we report Fe 3 O 4 @SiO 2 obtained by Stöber and sonochemical methods combination at low irradiation power (130 W, 1 h) with different volumes of tetraethylorthosilicate (TEOS). Fe 3 O 4 @SiO 2 results showed effects of diamagnetic silanol (Si-OH) layer as function of concentration over magnetic behavior. [ABSTRACT FROM AUTHOR]

Clustering superparamagnetic iron oxide nanoparticles (SPIONs) is one method of providing the biomedical benefits of larger SPIONs [e.g. superior T2 weighted magnetic resonance imaging (MRI) contrast] without increasing particle size. The work presented herein, describes the facile synthesis of clustered SPIONs that are suitable for MRI applications, by using a chitosan based polymer: N-palmitoyl -N- monomethyl -N- N-dimethyl -N- N -N- trimethyl-6-O-glycolchitosan (GCPQ) and aqueous nanoprecipitation followed by probe sonication, in the absence of organic solvents or elevated temperatures. The resulting clustered SPIONs consist of individual 8 nm iron oxide nanoparticles clustered into a 150 nm particle with a positive zeta potential (+23 mV) at neutral pH. X-ray diffraction confirms the presence of crystalline magnetic iron oxide, while magnetometer experiments show the clustered SPIONs are superparamagnetic giving an overall M s of 63.5 ± 1.3 emu g−1. Relaxometry analyses revealed that the clustered SPIONs (inclusive of coatings) had a high r 2 value of 294.8 mM−1 s−1 and an r 2 /r 1 of 21.1 making the clustered SPIONs suitable for T2 weighted (negative) MRI contrast imaging applications. The resulting clustered SPIONs demonstrate that highly sensitive T2 contrast agents may be produced in mild room temperature conditions, without the need for organic solvents or low molecular weight surfactants. [ABSTRACT FROM AUTHOR]

This study investigates the effect of SPIONs (superparamagnetic iron oxide nanoparticles, ∼12.5 nm in size) on summer squash plant (Cucurbita pepo) in the presence and absence of supplementary iron (Fe(II)-EDTA). The plants were grown in nutrient solution with different iron sources: (i) Fe(II)-EDTA, (ii) without Fe(II)-EDTA (iii) SPIONs only, and (iv) Fe(II)-EDTA with SPIONs. Plant growth and development were assessed after 20 days of soaking by measuring phenological parameters such as plant biomass, chlorophyll content, amount of carotenoids, and the catalase enzyme activity. Transmission electron microscopy, inductively coupled plasma atomic emission spectroscopy, X-ray diffraction, and vibrating sample magnetometer methods were used to detect uptake and translocation of SPIONs in plant tissues. Our results showed that SPIONs treatment (without Fe(II)-EDTA) caused growth retardation and decreased the plant biomass and chlorophyll content. Hence, they are not efficient sources to compensate for iron demand of squash plant. Electron microscopy observations, magnetization and elemental analyses revealed that SPIONs are taken-up by plant roots but not translocate to upper organs. In roots, SPIONs use a symplastic route for intercellular transfer. These findings suggest that as an iron source, SPIONs alone are not efficient for plant growth, but can contribute it together with Fe(II)-EDTA. • Superparamagnetic iron oxide nanoparticles (SPIONs, Fe 3 O 4 , ∼12.5 nm) and ionic iron (Fe(II)-EDTA) are subjected to squash. • SPIONs alone (without Fe(II)-EDTA) caused growth retardation and decreased plant biomass. • SPIONs are taken-up by plant roots but not translocate to aerial organs. • SPIONs alone are not efficient for plant growth, but can contribute it together with Fe(II)-EDTA. [ABSTRACT FROM AUTHOR]

Abstract Object The research follows the analysis of gellan gum-based gels as novel MRI phantom material with the implementation of a design of experiments model to obtain tunable relaxation properties. Materials and methods Gellan gum gels doped with newly synthesized superparamagnetic iron oxide nanoparticles (SPIONs) and either MnCl 2 or GdCl 3 were prepared and scanned from 230 μT to 3 T. Nineteen gel samples were formulated with varying concentrations of contrast agents to determine the linear, quadratic, and interactive effects of the contrast agents by a central composite design of experiment. To inhibit microbial growth in the gels and to enable long-term use, methyl 4‑hydroxybenzoate (methylparaben) was utilized. Results The model containing SPIONs and metal salts relaxivity was analyzed with ANOVA, and the resulting significant coefficients were tabulated. The mathematical model was able to accurately predict the intended relaxation property from the concentration of the contrast agent with adjusted R 2 values > 0.97 for longitudinal (R 1) relaxation rates and 0.87 for transverse (R 2) relaxation rates. Conclusion The gel material maintained physical, chemical, and biological stability for at least four months and contained controllable relaxation properties while maintaining optical clarity. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract Human colon cancer is one of the higher aggressive solid tumors, whose high mortality, much like many other solid tumors, results from metastasis formation. To reduce this high mortality, more effective chemotherapy, allowing a specific tumor accumulation and an efficient early-stage medical imaging as well, are still needed. At this regard, stimuli-responsive nanocarriers for anticancer drug delivery are promising strategy in cancer therapy. For this purpose, a dual targeted redox-responsive drug delivery system, prepared by coating superparamagnetic nanoparticles (SPIONs) with the amphiphilic copolymer INU-LA-PEG-FA and loading doxorubicin (DOXO-SPIONs) was investigated as tool for solid tumor chemotherapy. Folic acid (FA) has been chosen as active targeting agent as its receptor is upregulated in many tumors, including colon cancer. Lipoic acid (LA) has been used to act as the redox-responsive moiety, due to the presence of the -S-S- linkage into its structure, which can undergo intracellular reductive-induced cleavage, and therefore, a modification of stability and release profile of the nanocarrier. Accumulation by magnetic attraction was used as synergistic targeting strategy. Improved anticancer activity was demonstrated in mice by evaluating tumor volume reduction, immunohistochemical analyses and imaging properties using magnetic resonance imaging (MRI). [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract The extremely complex tumor microenvironment (TME) in humans is the major responsible for the therapeutic failure in cancer nanomedicine. A new concept of disease-driven nanomedicine, henceforth named "Theranomics", which attempts to target cancer cells and TME on the whole, represents an attractive alternative. Herein, a nanomedicine able to co-deliver doxorubicin and a tumor suppressive proteolytic protein such as collagenase-2 was developed. We successfully obtained superparamagnetic nanogels (SPIONs/Doco@Col) via the intermolecular azide-alkyne Huisgen cycloaddition. We demonstrated that a local ECM degradation and remodeling in solid tumors by means of collagenase-2 could enhance tumor penetration of nanomedicines and the in situ sustained release of the drug payload throughout 3-D tumor spheroids up to the core (parenchyma), thus enabling a synergistic and efficient anticancer effect toward highly invasive breast tumors. We illustrate that SPIONs/Doxo@Col is also capable of reducing the invasivity of cancer cells. [ABSTRACT FROM AUTHOR]

This study investigates the self-assembly of magnetic nanoparticles into a flat nanocomposite surface with concealed magnetic patterns. The application of a multilayer stamping medium and the presence of a magnetic field gradient would enable the attraction and organization of superparamagnetic iron oxide nanoparticles (SPIONs) onto predefined areas, corresponding to a pre-fabricated magnetic layer. The experimental approach involved preparing patterned surfaces by applying a multilayer of poly(ethyleneimine) (PEI) and poly(styrene sulfonate) (PSS) as a stamping medium. The SPIONs selectively adhered to the surface, mirroring the underlying magnetic layer shape. Subsequently, these SPION were subjected to an 80 °C treatment in the presence of an external magnetic field to enhance their magnetic properties, and then covered with a polystyrene layer. Using atomic force microscopy, magnetic force microscopy and dark field mode optical microscopy we demonstrated that obtained patterned magnetic field gradients are strong enough to attract and organize magnetic material on top of them, even when being covered with polymeric layers. Moreover, our findings show that the oriented deposition of magnetic nanoparticles is primarily determined by the strength of magnetic interactions between the pattern and nanoparticles, independently of surface topography (with roughness of 0.21 ± 0.06 nm) or Brownian motions. [Display omitted] [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • SPIONs functionalized with PEG and rhodamine with oligodendrocytes. • Dose effect and a maximum SPIONs loading on cells. • No toxicological and morphological influence. • No oxidative stress and inflammatory response. • Cells marked with SPIONs can be magnetically separated. Abstract Iron oxide nanoparticles have the capability to cross Blood Brain Barrier (BBB) and hence are widely investigated for biomedical operations in the central nervous system. Before being used for the biomedical purpose, it is necessary to investigate its biocompatibility, dosimetry and biological interaction. In the present study, in-house synthesized superparamagnetic iron oxide nanoparticles (SPIONs) were functionalized using the polymer, PolyEthylene Glycol (PEG) and a fluorophore (Rhodamine). The interaction of these nanoparticles with murine oligodendrocytes 158N was studied using different assays. The nanoparticles were taken up by the cells via endocytosis and there was a dose-dependent increase in the intracellular iron content as revealed by flow cytometry, transmission electron microscopy and confocal microscopy. Nanoparticles remained stable inside cells even after 24 h. Cell sorting capacity using a magnet depended on the number of particles interact per cell. SPIONs exhibited good biocompatibility as no toxicological responses, including morphological changes, loss of viability, oxidative stress or inflammatory response (IL-1β, IL-6 secretion) were observed. Together, these data show that the in-house synthesized SPIONs have no side effects on 158N cells, and constitute interesting tools for biomedical applications across brain, including cellular imaging and targeting. [ABSTRACT FROM AUTHOR]

Breast cancer chemotherapy can cause side effects due to nonspecific drug delivery, low solubility and fast metabolism of drugs used in conventional therapy. Moreover, the therapeutic effect of the drugs is often reduced by the strengthening of chemoresistance, which occurs via a variety of mechanisms. Different strategies have been developed to reduce multidrug resistance (MDR)-associated gene expressions including the use of surfactants and polymers. In this study superparamagnetic iron oxide nanoparticles (SPIONs) functionalized with conjugated linoleic acid (CLA) reduced the number and viability of cells in comparison with both untreated cells or cells treated with SPIONs alone. This cytostatic effect correlated with the increase of peroxisome proliferator-activated receptors γ (PPARγ). The necrotic cell death induced, as a consequence, an inflammatory process, as evidenced by the decrease of the anti-inflammatory PPARα and increase of pro-inflammatory TNFα and IL-1β. PPARs were examined because CLA is one of their natural ligands. The antitumor effect observed was accompanied by a down-regulation of p-glycoprotein (P-gp), which was the first important discovered efflux transporter belonging to MDR, and of ALDH3A1, an enzyme able to metabolize some drugs, reducing their effects. The down-regulation of P-gp correlated with the increase of cytokines. The ALDH3A1 decrease correlated with the increase of PPARγ. Based on these results, PPARs are molecular mediators of anti-cancer effect of SPIONs functionalized with CLA, being changes in these nuclear receptors correlated with induction of cytotoxicity and inflammation, and decreased ability of cancer cells in blocking anti-cancer drug effect. [ABSTRACT FROM AUTHOR]

Carboxymethyl Assam Bora rice starch coated superparamagnetic iron oxide nanoparticles (CM-ABRS SPIONs) were chemically synthesized by co-precipitation method and particle size reduction was controlled by high energy homogenization process. Effects of various process variables (polymer concentration, homogenization speed and cycles) were optimized on the basis of average particle size ( Z -average) and polydispersity index (PDI) of CM-ABRS SPIONs. The optimized CM-ABRS SPIONs were characterized for their particle size, surface morphology, electrokinetic potential, chemical interactions, crystallinity, magnetic properties, and targeting potential in presence of external magnetic field. In vitro localization of CM-ABRS SPIONs in a suspension of FITC (Fluorescein isothiocyanate) labeled RBCs (Red blood cells; hematocrit value; 45% (v/v)) was conducted inside a square glass capillary (500 × 500 μm 2 cross section) in the presence of an externally applied magnetic field (Ms = 150 mT), simulating the case of magnetic drug targeting (MDT) approach. The aggregation dynamics of CM-ABRS SPIONs inside a micro capillary was observed with respect to time ( t  = 0 to 600 s), which shows proportionality to time of exposure to the externally applied magnetic field. This in vitro study acts as an important platform for design and optimization of active targeted drug delivery system. [ABSTRACT FROM AUTHOR]

Superparamagnetic iron oxide nanoparticles (SPION) Fe 3 O 4 nanoparticles were prepared using different approaches: co-precipitation and sonochemical methods. This article is a comparative study on how different synthesis techniques greatly affect the magnetic properties and heating efficiency of such nanomaterial. Another important issue addressed here is the correlation between microstructure, colloidal stability, magnetization and specific absorption rate (SAR) of the nanoparticles. The results reveal that the sonochemical method for polyethylene glycol (PEGylated) Fe 3 O 4 with size 5 nm leads to pseudo single domain with smallest loop area. Additionally, large SAR values are obtained within 10–15 min using low magnetic field. [ABSTRACT FROM AUTHOR]

The response of cells to the exposure of nanomaterials is crucial for determining their safety in their multiple uses; however, the majority of the in vitro experiments use monolayered cell cultures instead of comparing the behavior of the cells in 3D, a more realistic environment. Here, we have analyzed how the exposed surface of the cells, as well as the environment where cells grow, can influence the interaction and uptake of superparamagnetic iron oxide nanoparticles (SPIONs). We exposed three different cell lines (MDAMB-231, HL60 and bEnd3), which grow at different environments, to increasing concentrations of SPIONs (0–150 µg·ml −1 ) and we evaluated parameters analyzing the morphological changes of the cell, iron uptake and cell viability. Results showed that upon exposure to SPIONs, cell viability and morphology are more affected when cells are growing in 3D systems, indicating that the increase of exposed surface area of the cells is a strong parameter to take in account when evaluating SPIONs or other materials or drugs. Our results clearly reinforce the use of more realistic environments, such as 3D, for the design of new drug delivery systems. [ABSTRACT FROM AUTHOR]

In this work, we report on a dual-behavior electrochemical/optical sensor for sensitive determination of Imidacloprid by fluorescent dye (fluorescein, FL) and imprinted polymer modified europium doped superparamagnetic iron oxide nanoparticles (FL@SPIONs@MIP). The imidacloprid (IMD)-imprinted polymer was directly synthesized on the Eu-SPIONs surface via Activators regenerated by the electron transfer-atom transfer radical polymerization (ARGET-ATRP) technique. Preparation, characterization and application of the prepared FL@SPIONs@MIP were systematically investigated using scanning electron microscopy (SEM), X-ray diffraction (XRD), vibrating sample magnetometer (VSM), fluorescence spectroscopy and electrochemical techniques. The electrochemical experiments exhibited a remarkable selectivity of the prepared sensor towards IMD. Determination of IMD by the square wave stripping voltammetry method represented a wide linear range of 0.059–0.791 μg L −1 with a detection limit of 0.0125 μg L −1 . In addition, the fluorescence method shows a linear range of 0.039–0.942 μg L −1 and LOD of 0.0108 μg L −1 . The fluorescence property of prepared FL@SPIONs@MIP was used for rapid, on-spot but selective detection of IMD in real samples. The proposed electrode displayed excellent repeatability and long-term stability and was successfully applied for quantitative and trace level determination of IMD in several real samples. [ABSTRACT FROM AUTHOR]

Here, we have studied the colloidal properties of carboxyl-amine functionalized superparamagnetic iron oxide nanoparticles (SPIONs with high saturation magnetization) based ferrofluids and their heating efficacies in magnetic fluid hyperthermia (MFH) via specific absorption rate (SAR)/intrinsic loss power (ILP). Moreover, we have systematically investigated the impact of the following heat influencing factors in MFH: (i) concentrations (0.5–8 mg/ml), (ii) surface coatings (trimesic acid (TMA), pyromellitic acid (PMA), terephthalic acid (TA) and aminoterephthalic acid (ATA)), (iii) applied alternating magnetic fields (AMFs - with amplitudes (H)/frequencies (f)) - chosen near to Hergt's biological safety limit, and (iv) dispersion media (biological/non-biological) for using SPIONs in in vitro cancer hyperthermia therapy. SPIONs (particularly decorated with dual-surfactants, i.e., TA-ATA) based aqueous ferrofluids have displayed excellent time-dependent temperature rise even at lower concentrations for the applied AMFs, which resulted in enhanced SAR values ranging from 12.5–200.1 W/g Fe because of their high colloidal stability and enhanced π-π conjugations from the close structural orientations of TA/ATA molecules due to high electrostatic attractions of the respective functional groups (-COOH/NH 2 ). Moreover, high ILP values of up-to 3.9 nHm 2 /kg (higher than the best commercial ferrofluids) are attained on exposure to magnetic fields below the safety limit. Besides, TA-ATA coated SPIONs dispersed in biological/non-biological media have exhibited better thermal responses as compared to their aqueous counterpart and reached therapeutic temperatures at faster rates due to prominent Neel relaxation mechanisms. The highest SAR value of 276.3 W/g Fe is recorded for TA-ATA coated SPIONs dispersed in triethylene glycol (TEG - with high viscosity), ascribed to the lesser inter-particle interactions from electrostatic repulsions of negative charges among carboxyl/oxygen molecules from SPIONs/TEG respectively. Moreover, TA-ATA coated SPIONs have induced almost 90% cell death in MCF-7 cancer cells in in vitro MFH studies. Thus, the TA-ATA coated SPIONs based ferrofluids have great potential for in vivo/clinical MFH cancer therapies. [ABSTRACT FROM AUTHOR]

The use of magnetic nanomaterials for the removal of toxic pollutants from water is currently gaining a considerable attention due to their low cost advantage and separation via the use of external magnetic field. However, for efficient functioning, these materials have to be structured in a way that will allow sufficient interaction with the pollutants within a shortest possible time. This can be achieved by employing very small sized nanomaterials such as nanoclusters which bear a very high surface energy and thus exhibit very rapid reactivity. In this report, ultrasmall-gluconic acid capped superparamagnetic iron oxide nanoclusters coprecipitated with goethite and hematite (USPIONCs-Goethem) were synthesized via a new cost-effective green approach and employed for the precipitation of neutral red from aqueous saline solution. The presence of goethite and hematite was verified using powder X-ray diffractiometry. The resulted magnetic- neutral red nanocomposite reassembled as sun-flowery-like nanostructure in the presence of an external magnetic field. A removal efficiency of about 92% was realized within a short time. This approach can be employed for the removal of other similar polyaromatic dyes bearing one or more lone-pair electron sites. [ABSTRACT FROM AUTHOR]

The subcellular distributions of nanoparticles in the brain are important for their biological application. We synthesized and characterized the superparamagnetic iron oxide nanoparticles (SPIONs) modified with poly (ethylene glycol) (PEG) and polyethylenimine (PEI) (PEG/PEI-SPIONs), and with dimyristoylphosphatidylcholine (DMPC) (DMPC-SPIONs). The nanoparticles were unilaterally injected into the left substantia nigra of rat brains. The distributions of the nanoparticles in the left brains of the rats were examined by ICP-OES (inductively coupled plasma optical emission spectrometer) and TEM (transmission electron microscopy) at 24 h after the injection. Iron was found in the olfactory bulb, temporal lobe, frontal cortex, thalamus and brain stem at 24 h after the injection of DMPC-SPIONs and PEG/PEI-SPIONs. In the rat substantia nigra, most DMPC-SPIONs were distributed in and on the myelin sheath around axons or on cell membranes, some were in cells. As a comparison, less iron was found in the rat brains at 24 h after the injection of PEG/PEI-SPIONs. Our experiments suggest DMPC modification on SPIONs be a safe and effective method for increasing SPIONs distribution on the cell membranes. This work is encouraging for further study on using DMPC-SPIONs for efficient drug delivery or for deep brain stimulation of neurons in a magnetic field. [ABSTRACT FROM AUTHOR]

Several blood replacements have been developed because of issues with blood collection and storage, increased expenditures, and a global lack of reserves. Studies on artificial blood primarily concentrate on the research and synthesis of molecules that transport oxygen. The primary objective of the current work was to create a supporting, oxygen-carrying biological material that can replace blood and be used to save lives when blood is not available. The work started with the synthesis of superparamagnetic iron oxide nanoparticles (SPIONS), and two distinct procedures were applied to ensure binding to hemoglobin (Hb) molecules. The surface modifications of the particles were carried out gradually by 3-amino propyl trimethoxy silane (3APGASPIONS) and tartaric acid (TASPIONS). Analysis methods used to characterize the particles include Fourier transform infrared spectrophotometer (FT-IR), elemental analysis (EDX), scanning electron microscope (SEM), X-ray diffractometry (XRD), and high contrast transmission electron microscopy (C-TEM). The characterization studies of SPIONS which bind Hb molecules to the surface were repeated and their effects on endothelial cell culture were examined to determine their toxic effects in vitro. Cell proliferation, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activity changes were assessed in the evaluation of the possible toxic effects of the cells against the treated particles in the prepared cell lines. Blood substitute solutions synthesized by two different methods were stored on the shelf for about 1 month and the results were compared with fresh Hb solutions. The CV and UV analysis results obtained from artificial Hb substitutes revealed that the structural integrity of Hb molecules did not change, the oxygen transport capabilities of biomolecules were preserved, and this state remained stable for a long time. Furthermore, it was determined that nanocomplexes synthesized by the two methods caused different cellular proliferation and there was a more limited increase in cellular enzyme activities (SOD, CAT, GPx) of Hb-bound particle solutions when compared to pure SPIONS. [ABSTRACT FROM AUTHOR]

Singlet oxygen is a dominant reactive oxygen species that determine the fate of photodynamic therapy efficacy. We herein report the singlet oxygen generation potential of a newly synthesized superparamagnetic iron oxide nanoparticles-gold core-shell porphyrin conjugate prepared for the purpose of achieving magnetically-driven porphyrin structure. Successful conjugation was achieved via encapsulation within thiolated methoxy polyethylene glycol matrix following solvent evaporation approach. The magnetic PEGylated porphyrin nano-construct was characterized using optical absorption, transmission electron microscopy (TEM) and zeta potential techniques. The as-synthesized porphyrin conjugate emits red and near-infrared light at various excitations from ultraviolet to visible, shows strong attraction towards external magnetic field and exhibits high singlet oxygen generation potential. [ABSTRACT FROM AUTHOR]

A multifunctional nanomedicine platform was designed and evaluated for efficient colon cancer therapy by a combinatorial therapeutic approach based on a chemotherapeutic drug and mild hyperthermia. Advantage was taken from the dual role of methotrexate (MTX), as folate receptor-targeting, overexpressed in tumor cells, and as anticancer drug. Incorporation of superparamagnetic iron oxide nanoparticles (SPIONs) allows to heat cancer cells externally through an alternating magnetic field. The developed nanocarrier was based on polyethylene glycol–polylactic acid (PEG-PLA) nanospheres to improve biocompatibility, enhancing their targeting by prolonging blood circulation time. By an emulsion-evaporation method the nanospheres were produced and then characterized for size distribution, zeta-potential, in vitro drug release profile and cellular studies. The co-delivery of MTX and SPIONs on PEG-PLA nanospheres resulted in nanocarriers with a size of 160 nm in diameter, a polydispersity index below 0.2 and a zeta potential of ca. − 18 mV. Multifunctional nanospheres were monodisperse and stable up to 3 months. MTX was released preferentially under mild hyperthermia conditions. The multifunctional nanospheres were able to increase the cytotoxicity of MTX towards Caco-2 and SW-480 colon cancer cells, in comparison to free drug. Also, the nanospheres allowed the incorporated MTX to induce greater cell cycle arrest and apoptotic effects than the free MTX. This study provides evidences that MTX-SPIONs-PEG-PLA nanospheres are a promising solution to address colorectal cancer over-expressing folate receptors, by a combinatory approach. [ABSTRACT FROM AUTHOR]

The combination of imaging and delivery systems through nanoscale material have been used to create new nanoparticle formulations for biological applications. Here, a magnetic nanocomposite consisting of superparamagnetic iron oxide nanoparticles (SPIONs), graphene oxide (GO), chitosan and poly(vinyl alcohol) (PVA) as biocompatible polymers was synthesized for applying in drug delivery and imaging agent. The nanocomposite was studied by various techniques including XRD, TEM, FE-SEM, FT-IR and VSM. SPIONs had an average diameter size about 10 nm and showed superparamagnetic behavior. Also, TEM and SEM images showed that these nanoparticles successfully attached on the surface of GO sheets. Finally, 5-fu was loaded onto these nanocomposite particles in order to study of entrapment efficiency and drug release behavior of nanocomposite particles. They showed high drug entrapment efficiency and more and faster drug release in acidic pH. [ABSTRACT FROM AUTHOR]

We demonstrate microfluidic switching valves using magnetic nanoparticles blended within the working fluid as an alternative microfluidic flow control in microchannels. Y-shaped microchannels have been fabricated by using a CO 2 laser cutter to pattern microchannels on transparent poly(methyl methacrylate) (PMMA) sheets covered with thermally bonded transparent polyvinyl chloride (PVC) sheets. To examine the performance of the microfluidic magnetic switching valves, an aqueous magnetic nanoparticle suspension was injected into the microchannels by a syringe pump. Neodymium magnets were then employed to attract magnetic nanoparticles and form an aggregate that blocked the microchannels at a required position. We have found that the maximum volumetric flow rate of the syringe pump that the magnetic nanoparticle aggregate can withstand scales with the square of the external magnetic flux density. The viscosity of the fluid exhibits dependent on the aggregate length and the size of the magnetic nanoparticles. This microfluidic switching valve based on aggregates of magnetic nanoparticles has strong potentials as an on-demand flow control, which may help simplifying microfluidic channel designs. [ABSTRACT FROM AUTHOR]

Monodispersed SPIONs (superparamagnetic iron oxide nanoparticles) co -coated with PEG and PEI polymers were prepared by an improved polyol method. To accomplish cancer-specific targeting properties, FA (folic acid) was then modified on the SPIONs via EDC/NHS method (FA-SPIONs). Doxorubicin (DOX) as an example anticancer drug was loaded within FA-SPIONs (DOX@FA-SPIONs), the DOX release rate of DOX@FA-SPIONs was much high in low pH PBS. The SPIONs, FA-SPIONs and DOX@FA-SPIONs with mean hydrodynamic diameters of 23, 40 and 67 nm, respectively, performed excellent colloidal stability in PBS. Confocal laser scanning microscope (CLSM) study implicates that the DOX@FA-SPIONs target MCF-7 cells efficiently through the FA receptor-mediated endocytosis. DOX@FA-SPIONs were tested in nude mice with xenograft MCF-7 breast tumor though tail intravenous injection and were found inhibiting tumor growth more efficiently. The application of a magnetic field (MF) greatly improved the growth inhibiting efficiencies of DOX@FA-SPIONs on MCF-7 cells in vitro and on xenograft MCF-7 breast tumor of nude mice in vivo. The aggregation of SPIONs in tumor was monitored by magnetic resonance imaging (MRI) as the DOX@FA-SPIONs exhibited high r 2 relaxivity (81.77 mM − 1 S − 1 ). Histology on liver, Lung, kidney and heart in mice showed no significant toxicity of DOX@FA-SPIONs on mice organs after 35-day treatment. The FA-SPIONs are a high efficient drug delivery nanoplatform for advanced cancer theranostics. [ABSTRACT FROM AUTHOR]

There is a growing need for alternatives to target and treat bacterial infection. Thus, the present work aims to develop and optimize the production of PEGylated magnetoliposomes (MLPs@PEG), by encapsulating superparamagnetic iron oxide nanoparticles (SPIONs) within fusogenic liposomes. A Box–Behnken design was applied to modulate size distribution variables, using lipid concentration, SPIONs amount and ultrasonication time as independent variables. As a result of the optimization, it was possible to obtain MLPs@PEG with a mean size of 182 nm, with polydispersity index (PDI) of 0.19, and SPIONs encapsulation efficiency (%EE) around 76%. Cytocompatibility assays showed that no toxicity was observed in fibroblasts, for iron concentrations up to 400 μ g /ml. Also, for safe lipid and iron concentrations, no hemolytic effect was detected. The fusogenicity of the nanosystems was first evaluated through lipid mixing assays, based on Förster resonance energy transfer (FRET), using liposomal membrane models, mimicking bacterial cytoplasmic membrane and eukaryotic plasma membrane. It was shown that the hybrid nanosystems preferentially interact with the bacterial membrane model. Confocal microscopy and fluorescence lifetime measurements, using giant unilamellar vesicles (GUVs), validated these results. Overall, the developed hybrid nanosystem may represent an efficient drug delivery system with improved targetability for bacterial membrane. [Display omitted] • MLPs@PEG production was modulated and optimized with a Box–Behnken design. • Cytocompatibility studies showed that the lipid coverage reduces SPIONs' toxicity. • No hemolytic activity was detected. • MLPs@PEG preferentially interact with bacterial membrane models (LUVs and GUVs). [ABSTRACT FROM AUTHOR]

Polymer encapsulation of raw ferrofluids was carried out by free radical emulsion polymerization using macro-RAFT copolymers as stabilizers. The iron oxide cores with positively charged surface at the pH of encapsulation were dispersed in a solution of negatively charged random macro-RAFT copolymer by ultrasonication. Uniform polymer encapsulated super paramagnetic iron oxide nanoparticles (SPIONs) were produced by feeding the mixture of methyl methacrylate (MMA) and n -butyl acrylate (BA) monomers into the dispersion containing water soluble initiator 4,4’-azobis (4-cyanopentanoic acid) (V501). Shell thickness could be controlled by adjusting the amount of coating monomer added. Polymer encapsulation of SPIONs aligned in a magnetic field produced polymer encapsulated SPION rods. Monodispersed sterically stabilized crosslinked polymer encapsulated SPIONs were synthesized using diblock and random macro-RAFT copolymers as stabilizers. Rhodamine labeled SPIONs were found to be non-cytotoxic and suitable for cell labeling. [ABSTRACT FROM AUTHOR]

Hybrid magnetic nanoparticles based on poly(methylmethacrylate) (PMMA) and super-paramagnetic iron oxide nanopaticles (SPIONs) with selective surface modification has been developed for heavy metal removal by applying external magnetic fields. The nanoparticles were prepared by the emulsion polymerization technique in an aqueous suspension of SPIONs. The hydrolysis of carboxyl functional group was then applied for grafting polyethylene glycol bis(amine)(PEG-bis(amine)) onto the PMMA-coated SPIONs. The morphology, the chemical structure and the magnetic properties of the grafted nanoparticles were investigated. The efficiency of the hybrid nanoparticles for heavy metal removal were conducted on Pb(II), Hg(II), Cu(II) and Co(II) in aqueous solutions.The metal concentration in the solutions after separation by the hybrid nanoparticles was determined by inductively coupled plasma optical emission spectrometer (ICP-OES). The results show the heavy metal uptake ratios of 0.08, 0.04, 0.03, and 0.01 mM per gramme of the grafted SPIONs for Pb(II), Hg(II), Cu(II), and Co(II), respectively. A competitive removal of Cu(II), Pb(II), Co(II) and Hg(II) ions in mixed metal salt solutions has also been studied.The heavy metal removal efficiency of the hybrid nanoparitcles was found to depend on the cation radius, in accordance with capture of metal ions by the amine group. [ABSTRACT FROM AUTHOR]

Extensive use of superparamagnetic iron oxide nanoparticles (SPIONS) in theranostics prompted us to investigate the acute changes in cell morphology and function following intravenous administration of surface-modified SPIONS in a rat model. Dextran-coated (DEX) and polyethylene glycol-coated (PEG) SPIONS were synthesized and characterized, and cytocompatibility was evaluated in vitro. Haematological, histopathological, ultrastructural and oxidative stress analyses were carried out 24 h post intravenous administration in vivo. In test groups, SGPT and SGOT enzymes were significantly altered when compared to saline-only controls. Anti-oxidant imbalance and lipid peroxidation were observed in all major organs. Histology revealed iron-laden Kupffer cells and macrophages in liver and lung respectively. Iron overload was observed in the convoluted tubules of the kidney. Mast cell infiltration and distribution were observed differentially in test groups. Although surface modification of SPIONS improved biocompatibility in vitro, they affected anti-oxidant and tissue nitrite levels, which greatly influenced mast cell infiltration in vivo. [ABSTRACT FROM AUTHOR]

This study was designed to use superparamagnetic iron oxide nanoparticles (SPIONs) as evaluating tools to study monocyte-derived macrophages (MDM)-mediated delivery of small molecular agents into the diseased brains. MDM were tested with different-configured SPIONs at selected concentrations for their impacts on carrier cells’ physiological and migratory properties, which were found to depend largely on particle size, coating, and treatment concentrations. SHP30, a SPION of 30-nm core size with oleic acids plus amphiphilic polymer coating, was identified to have high cellular uptake efficiency and cause little cytotoxic effects on MDM. At lower incubation dose (25 μg/mL), few alteration was observed in carrier cells’ physiological and in vivo migratory functions, as tested in a lipopolysaccharide-induced acute neuroinflammation mouse model. Nevertheless, significant increase in monocyte-to-macrophage differentiation, and decrease in in vivo carrier MDM inflamed-brain homing ability were found in groups treated with a higher dose of SHP30 at 100 μg/mL. Overall, our results have identified MDM treatment at 25 μg/mL SHP30 resulted in little functional changes, provided valuable parameters for using SPIONs as evaluating tools to study MDM-mediated therapeutics carriage and delivery, and supported the concepts of using monocytes-macrophages as cellular vehicles to transport small molecular agents to the brain. [ABSTRACT FROM AUTHOR]

Superparamagnetic iron oxide nanoparticles (SPIONs) are highly cytotoxic and target cancer cells with high specificity; however, the mechanism by which SPIONs induce cancer cell-specific cytotoxicity remains unclear. Herein, the molecular mechanism of SPION-induced cancer cell-specific cytotoxicity to cancer cells is clarified through DNA microarray and bioinformatics analyses. SPIONs can interference with the mitochondrial electron transport chain (METC) in cancer cells, which further affects the production of ATP, mitochondrial membrane potential, and microdistribution of calcium, and induces cell apoptosis. Additionally, SPIONs induce the formation of reactive oxygen species in mitochondria; these reactive oxygen species trigger cancer-specific cytotoxicity due to the lower antioxidative capacity of cancer cells. Moreover, the DNA microarray and gene ontology analyses revealed that SPIONs elevate the expression of metallothioneins in both normal and cancer cells but decrease the expression of METC genes in cancer cells. Overall, these results suggest that SPIONs induce cancer cell death by targeting the METC, which is helpful for designing anti-cancer nanotheranostics and evaluating the safety of future nanomedicines. [ABSTRACT FROM AUTHOR]

To improve the sensitive and specific detection of metastasis of lung cancer, this study fabricated immune superparamagnetic iron oxide nanoparticles (SPIONs) used in magnetic resonance (MR) immumoimaging. These SPIONs were coated with oleic acid and carboxymethyl dextran, and then conjugated to mouse anti-CD44v6 monoclonal antibody. The physicochemical properties of magnetic nanoparticles without monoclonal antibody were characterized by X-ray powder diffraction (XRD), thermogravimetric analysis (TGA), and Fourier transform infrared spectroscopy (FTIR). The sizes of the nanoparticles were determined by dynamic light scattering measurements (DLS) and transmission electron microscope (TEM). Coated nanoparticles could well disperse in water with low dosage of CMD as the Fe/CMD ratio is 1/1 and 2/1 (w/w). Importantly, these SPIONs have relatively high saturation magnetization, as measured by vibrating sample magnetometer (VSM). They could efficiently become the transversal relaxation times (T2) contrast agent to improve detection limit through measured in vitro magnetic resonance imaging (MRI) and actively target human lung adenocarcinoma (A549) cells in vitro cell culture. Thus, these immune SPIONs are potentially useful for lung tumor-targeting diagnosis. [ABSTRACT FROM AUTHOR]

Treatment for metastatic breast cancer still remains to be a challenge since the currently available diagnostic and treatment strategies fail to detect the micro-metastasis resulting in higher mortality rate. Moreover, the lack of specificity to target circulating tumor cells is also a factor. In addition, currently available imaging modalities to identify the secondaries vary with respect to various metastatic anatomic areas and size of the tumor. The drawbacks associated with the existing clinical management of the metastatic breast cancer demands the requirement of multifunctional nanotheranostics, which could diagnose at macro- and microscopic level, target the solid as well as circulating tumor cells and control further progression with the simultaneous evaluation of treatment response in a single platform. However, without the understanding of the biology as well as preferential homing ability of circulating tumor cells at distant organs, it is quite impossible to address the existing challenges in the present diagnostics and therapeutics against the breast cancer metastasis. Hence this review outlines the severity of the problem, basic biology and organ specificity with the sequential steps for the secondary progression of disease followed by the various mechanistic approaches in diagnosis and therapy at different stages. [ABSTRACT FROM AUTHOR]

[Display omitted] Superparamagnetic iron nanoparticles (SPIONs) have become one of the most useful colloidal systems in nanomedicine. We report here the preparation of new hybrid core@shell systems based on SPION nanoparticles coated with a SiO 2 shell (SPION@SiO 2) and functionalized with carboxyl groups (SPION@SiO 2 -COOH). A series of new N -alkylamino- and N -alkylamido-terminated 1-phenyl- tetrahydroisoquinolines (THIQs) and 3-tetrahydrobenzazepines (THBs) derivatives presenting -SMe and -Cl groups, respectively, with potential dopaminergic activity, are synthesized and incorporated to the hybrid system. We include the synthetic details for THIQs and THBs derivatives preparation and investigate the influence of the terminal-functional group as well as the number of carbon atoms linked to THIQ and THB molecules during the coupling to the SPION@SiO 2 -COOH. Nuclear magnetic resonance (NMR) and electron ionization mass spectrometry (EI-MS) are used to characterize the synthesized THIQs and THBs. High-angle annular dark-field transmission electron microscopy (HAADF-TEM), energy dispersive X-ray transmission electron microscopy (EDX-TEM), and proton high-resolution magic angle spinning NMR spectroscopy1H HRMAS-NMR) are used to confirm the presence of THB and THIQ molecules onto the surface of the nanoparticles. The hybrid SPION@SiO 2 -THIQ and THB systems show significant activity toward the D 2 receptor, reaching Ki values of about 20 nM, thus having potential application in the treatment of central nervous system (CNS) diseases. [ABSTRACT FROM AUTHOR]

The potential toxicity of CoFe 2 O 4 nanobeads (NBs) in Chlorella vulgaris was observed up to 72 h. Algal cell morphology, membrane integrity and viability were severely compromised due to adsorption and aggregation of NBs on algal surfaces, release of Fe 3+ and Co 2+ ions and possible mechanical damage by NBs. Interactions with NBs and effective decrease in ions released by aggregation and exudation of algal cells as a self defense mechanism were observed by Fourier transform infrared attenuated total reflectance (FTIR-ATR) and inductively coupled plasma mass spectrometry (ICP-MS). The results corroborated CoFe 2 O 4 NBs induced ROS triggered oxidative stress, leading to a reduction in catalase activity, activation of the mutagenic glutathione s-transferase ( mu -GST) and acid phosphatase (AP) antioxidant enzymes, and an increase in genetic aberrations, metabolic and cellular signal transduction dysfunction. Circular dichroism (CD) spectra indicated the weak interactions of NBs with BSA, with slight changes in the α-helix structure of BSA confirming conformational changes in structure, hence the potential for functional interactions with biomolecules. Possible interferences of CoFe 2 O 4 NBs with assay techniques and components indicated CoFe 2 O 4 NBs at lower concentration do not show any significant interference with ROS, catalase, mu -GST and no interference with CD measurements. This study showed ROS production is one of the pathways of toxicity initiated by CoFe 2 O 4 NBs and illustrates the complex processes that may occur between organisms and NBs in natural complex ecosystem. [ABSTRACT FROM AUTHOR]

Nanotechnology represents a major frontier with potential to significantly advance the field of bone tissue engineering. Current limitations in regenerative strategies include impaired cellular proliferation and differentiation, insufficient mechanical strength of scaffolds, and inadequate production of extrinsic factors necessary for efficient osteogenesis. Here we review several major areas of research in nanotechnology with potential implications in bone regeneration: 1) nanoparticle-based methods for delivery of bioactive molecules, growth factors, and genetic material, 2) nanoparticle-mediated cell labeling and targeting, and 3) nano-based scaffold construction and modification to enhance physicochemical interactions, biocompatibility, mechanical stability, and cellular attachment/survival. As these technologies continue to evolve, ultimate translation to the clinical environment may allow for improved therapeutic outcomes in patients with large bone deficits and osteodegenerative diseases. From the Clinical Editor Traditionally, the reconstruction of bony defects has relied on the use of bone grafts. With advances in nanotechnology, there has been significant development of synthetic biomaterials. In this article, the authors provided a comprehensive review on current research in nanoparticle-based therapies for bone tissue engineering, which should be useful reading for clinicians as well as researchers in this field. [ABSTRACT FROM AUTHOR]

The formation and deposition of proteinaceous aggregates of amyloid fibrils characterize diverse degenerative diseases, such as Alzheimer's, Parkinson's, and systemic amyloidosis. The presence of these aggregates is associated with clinical manifestations, and various forms of amyloid aggregates have been identified to be cytotoxic. Although the exact mechanism of amyloid toxicity remains to be elucidated, prevention of amyloid fibril formation and aggregation forms a possible therapeutic approach. Nanomaterials possess the potential for such a strategy. Using hen egg white lysozyme (HEWL) as a prototypic amyloid-forming protein, we found a reduction in the aggregation rate of HEWL in the presence of super-paramagnetic iron oxide nanoparticles (SPIONs) with slowing of nucleation and amyloid fibril elongation. HEWL-amyloid had a predominantly fibrillar structure and was toxic to various cells. A significant attenuation of cytotoxicity was observed when cells were treated with SPION-interacted HEWL-amyloid. Ultra-structural differences were observed between the native and SPION-interacted HEWL-amyloids by SEM and TEM imaging. Our findings confirm that SPIONs perturb amyloid fibrillation, thereby reducing the cytotoxicity of amyloid. [ABSTRACT FROM AUTHOR]

This paper deal with the synthesis and characterization of PEGylated squalene-grafted-inulin amphiphile capable of self-assembling and self-organizing into nanocarriers once placed in aqueous media. It was exploited as coating agent for obtaining doxorubicin loaded superparamagnetic iron oxide nanoparticles (SPIONs) endowed with stealth like behavior and excellent physicochemical stability. Inulin was firstly modified in the side chain with primary amine groups, followed in turn by conjugation with squalenoyl derivatives through common amidic coupling agents and PEGylation by imine linkage. Polymer coated SPIONs were so obtained by spontaneous self-assembling of inulin copolymer onto magnetite surface involving hydrophobic–hydrophobic interactions between the metallic core and the squalene moieties. The system was characterized in terms of hydrodynamic radius, zeta potential, shape and drug loading capacity. On the whole, the stealth-like shell stabilized the suspension in aqueous media, though allowing the release of the doxorubicin loaded in therapeutic range. The cytotoxicity profile on cancer (HCT116) cell line and in vitro drug uptake were evaluated both with and without an external magnetic field used as targeting agent and uptake promoter, displaying that magnetic targeting implies advantageous therapeutic effects, that is amplified drug uptake and increased anticancer activity throughout the tumor mass. [ABSTRACT FROM AUTHOR]

Abstract: Nano-sized curcumin-loaded super-paramagnetic iron oxide nanoparticles (CUR-OA-SPIONs) were synthesized chemically by co-precipitation method using oleic acid as a stabilizer and Myrj 52 as a surfactant. The synthesized nanoparticles were characterized for their shape, size, surface morphology, electrokinetic potential, magnetic properties, crystalinity, chemical interactions and thermal transitions. The synthesized CUR-OA-SPIONs were spherical, mono-dispersed, physically stable and super-paramagnetic in nature. In vitro localization study and aggregation dynamics of CUR-OA-SPIONs were studied with a flow of blood inside a square glass capillary (500×500μm2 cross section) in the presence of an externally applied magnetic field (Ms=1200mT). This research which is first of its kind showed the fluorescent imaging of CUR-OA-SPIONs with respect to time to understand the aggregation dynamics of magnetic nanoparticles in a micro capillary simulating the case of targeted drug delivery system. The size of the aggregation increases with respect to time (t =0+ s to t =500s), while no significant change in the size of the aggregate was observed after time t =500s. [Copyright &y& Elsevier]

Abstract: Superparamagnetic iron oxide nanoparticles (SPIONs) are of great interest in nanomedicine due to their capability to act simultaneously as a contrast agent and as a targeted drug delivery system. At present, one of the biggest concerns about the use of SPIONs remains around its toxicity and, for this reason, it is important to establish the safe upper limit for each use. In the present study, SPION coated with cross-linked aminated dextran (CLIO-NH2) were synthesized and their toxicity to zebrafish brain was investigated. We have evaluated the effect of different CLIO-NH2 doses (20, 50, 100, 140 and 200mg/kg) as a function of time after exposure (one, 16, 24 and 48h) on AChE activity and ache expression in zebrafish brain. The animals exposed to 200mg/kg and tested 24h after administration of the nanoparticles have shown decreased AChE activity, reduction in the exploratory performance, significantly higher level of ferric iron in the brains and induction of casp8, casp 9 and jun genes. Taken together, these findings suggest acute brain toxicity by the inhibition of acetylcholinesterase and induction of apoptosis. [Copyright &y& Elsevier]

Highlights: [•] A novel, stable and powerful nano Pd-NHC complex was synthesized. [•] We examined Mizoroki–Heck and Suzuki–Miyaura cross coupling reactions with extremely low palladium loading. [•] These cross coupled products were produced in excellent yields under conventional heating and microwave irradiation. [•] The nano-Pd-NHC catalyst shows high turnover frequencies. [•] The catalyst was recovered by external magnetic field and was reused for seven reaction cycles. [Copyright &y& Elsevier]

Abstract: Superparamagnetic iron oxide nanoparticles (SPIONs) have been proposed for use in magnetic resonance imaging as versatile ultra-sensitive nanoprobes for Alzheimer's disease imaging. In this work, we synthetized an efficient contrast agent of Alzheimer's disease using 1,1-dicyano-2-[6-(dimethylamino)naphthalene-2-yl]propene (DDNP) carboxyl derivative to functionalize the surface of SPIONs. The DDNP-SPIONs are prepared by conjugating DDNP carboxyl derivative to oleic acid-treated SPIONs through ligand exchange. The structure, size distribution and magnetic property were identified by IR, TGA–DTA, XRD, TEM, Zetasizer Nano and VSM. TEM and Zetasizer Nano observations indicated that the DDNP-SPIONs are relatively mono-dispersed spherical distribution with an average size of 11.7nm. The DDNP-SPIONs were then further analyzed for their MRI relaxation properties using MR imaging and demonstrated high T2 relaxivity of 140.57s−1FemM−1, and the vitro experiment that DDNP-SPIONs binding to β-Amyloid aggregates were then investigated by fluorophotometry, the results showed that the combination had induced the fluorescence enhancement of the DDNP-SPIONs and displayed tremendous promise for use as a contrast agent of Alzheimer's disease in MRI. [Copyright &y& Elsevier]

• Superparamagnetic Iron oxide nanoparticles (SPIONs) were synthesized using Pimenta dioica leaf extract. • In-vitro cytotoxicity assay on HeLa cells shows the biocompatibility of SPIONs. • SPIONs showed potential to be used as a green alternative of contrast agents for OCT. • Green synthesized SPIONs efficiently produced magnetic hyperthermia responses on HeLa, cancerous cells. A green chemistry-based approach to nanoparticle synthesis is an eco-friendly, simple, and cost-effective way to fabricate nanoparticles. This study aims at the biomedical applications of green synthesized near-infrared (NIR) active superparamagnetic iron oxide nanoparticles (SPIONs). The SPIONs obtained by the green synthesis route are non-toxic and their surface is free from any chemical impurity. The MTT [3-(4, 5-Dimethylthiazol-2-yl)-2, 5-Diphenyltetrazolium Bromide] assay was accomplished on human cervical cancer (HeLa) cells and shows that the SPIONs are biocompatible and thus safe for cells even at higher concentrations up to 500 μg/ml. The synthesized SPIONs display an absorbance in the tissue transparent NIR wavelength region. The SPIONs exhibit a superparamagnetic behavior with high saturation magnetization of 66 emu/g. Owing to their excellent optical and magnetic properties, the potential of these green synthesized SPIONs as an exogenous contrast agent in deep-tissue magnetomotive optical coherence tomography (MM-OCT) imaging was evaluated ex-vivo using chicken breast tissue. A significant enhancement in the contrast and the penetration depth was observed with time. The heating response of green synthesized SPIONs was evaluated under the application of an external magnetic field. The results suggest that these SPIONs could be used as theranostic agents for deep tissue biomedical imaging and therapeutic applications. [ABSTRACT FROM AUTHOR]

Abstract: Short interfering RNAs (siRNAs) can downregulate the synthesis of proteins and thus be used to treat certain diseases where the protein synthesis is upregulated, such as cancer. The challenge is to deliver siRNAs in the target cell as they are rapidly degraded by nucleases and have difficulties to cross the cellular membranes. Superparamagnetic iron oxide nanoparticles (SPIONs) are widely studied as platforms for smart biocompatible nanosystems which can be used for magnetic drug targeting and magnetic resonance imaging. The aim of this work was to combine siRNAs, SPIONs, and chitosan, to develop new magnetic siRNA nanovectors suitable for systemic administration. In a first time, the one factor at a time (OFAT) methodology was used to adjust different formulation parameters and to test the feasibility of such a formulation. In a second time, design of experiment (DOE) methodology was used to analyze the influence of these formulation parameters on the physicochemical characteristics hydrodynamic diameter (D H) and ζ-potential. Finally, four MSNs suitable for systemic administration could be identified using the OFAT method. The DOE method showed a significant effect of CR and [NaNO3] on the D H and a significant effect of MR and [siRNA] on the ζ-potential of the nanocarriers. [Copyright &y& Elsevier]