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Background: 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. Methods: 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. Results: 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. Conclusions: 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.

Background: 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. Methods: 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. Results and Conclusion: 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.

Due to unique reaction conditions of the acoustic cavitation process, ultrasound-assisted synthesis of nanoparticles has attracted increased research attention. In this study, we demonstrate the effect of ultrasonic irradiation on the crystallinity, stability, biocompatibility, and magnetic properties of chitosan-coated superparamagnetic iron oxide nanoparticles (CS-SPIONs). CS solution and colloidal suspension of SPIONs were mixed and sonicated using an ultrasonic probe of 1.3 cm tip size horn, frequency (20 kHz), and power (750 W). Different samples were sonicated for 1.5, 5, and 10 min with corresponding acoustic powers of 67, 40 and 36 W, and the samples were denoted S1.5, S5, and S10, respectively. The samples were characterized using X-ray diffractometer (XRD), Energy dispersive X-ray (EDX), Transmission electronic microscope (TEM), Fourier transform infrared spectroscopy (FTIR), Zeta sizer, and vibrating sample magnetometer (VSM). Cell cytotoxicity and cell uptake were investigated with human embryonic kidney 293 (HEK-293) cells through MTT assay and Prussian blue staining, respectively. The sharp peaks of the XRD pattern were disappearing with an increase in the sonication period but a decrease in acoustic power. EDX analysis also demonstrates that atomic and weight percentages of the various elements in the samples were decreasing with an increase in the sonication period. However, the Zeta potential (ζ) values increase with an increase in the sonication period.The saturation magnetization (Ms) of the S1.5 before and after the coating is 62.95 and 86.93 emu/g, respectively. Cell cytotoxicity and uptake of the S1.5 show that above 70% of cells were viable at the highest concentration and the longest incubation duration. Importantly, the CS-SPIONs synthesized by the sonochemical method are non-toxic and biocompatible.

Bioactive glasses and glass-ceramics are well-proven potential biomaterials for bone-tissue engineering applications because of their compositional flexibility. Many research groups have been focused to explore the utility of bioactive glass–ceramics beyond bone engineering to hyperthermia treatment of cancer. Hyperthermia refers to raising the temperature of tumor close to 44°C at which malignant cells perish with negligible harm to normal cells. Hyperthermia can be employed by many means such as by ultrasonic waves, electromagnetic waves, infrared radiations, alternating magnetic fields, etc. Magnetic bioactive glass–ceramics are advantageous over other potential candidates for thermoseeds such as nanofluids, superparamagnetic nanoparticles because they can bond not only to the natural bone but also with soft tissues in few cases, which helps regenerating the affected part due to its bioactive nature. Strict restrictions on clinical settings (H×f< 5×109) force the research activities to be more focused on material characteristics to raise the implant temperature to required ranges. Lots of efforts have been made in past years to tackle these challenges and design best-suited glass–ceramics for hyperthermia treatment. This review aims to provide essential information on the concept of hyperthermia treatment of cancer and recent developments in the field of bioactive glass–ceramics for cancer treatment. The advantages and disadvantages of magnetic glass–ceramics over other potential thermoseed materials are highlighted. In this field, the major challenges are to develop magnetic glasses, which have fast and bulk crystallization with optimized magnetic phases with lower Curie and Neel temperatures.

Superparamagnetic Iron Oxide Nanoparticles (SPIONs) remains as a subject of extensive research in modern days due to their significant role in environmental remediation. The current study deals with SPIONs in removal of textile effluent dye, crystal violet. Three different types of SPIONs (SPIONs – a, b, c) were synthesized by chemical co-precipitation method having sodium hydroxide as reducing agent. The synthesized SPIONs were characterized by Fourier Transform Infrared Spectroscopy (FT-IR), Scanning Electron Microscopy (SEM), Energy-Dispersive X-ray Spectroscopy (EDX) and X-ray Diffraction (XRD). All the produced SPIONs were crystalline. Amongst them, the smallest and the best adsorbing SPIONs (SPIONs-a) against crystal violet dye was identified . SPIONs-a was found to possess super paramagnetism and of size below 50 ​nm. The adsorption efficiency by SPIONs-a were optimized for adsorbate-adsorbent concentration where it was found to be 8 ​g/L SPIONs-a, pH 9 and 2 ​h time of contact. It was subjected for mathematical models like Langmuir, Freundlich and Temkin isotherms studies which states the interaction of adsorbent and adsorbate. It was found to remove 94.7% CV and it was relevance with Temkin isotherms.

Heart failure (HF) is a multifactorial, heterogeneous systemic disease that is considered one of the leading causes of death and morbidity worldwide. It is well-known that endothelial dysfunction (ED) plays an important role in cardiac disease etiology. A reduction in the bioavailability of nitric oxide (NO) in the bloodstream leads to vasoconstriction and ED. Many studies indicated diminishment of peripheral arteries vasodilation that is mediated by the endothelium in the of patients with chronic HF. With the advancement of nanomedicine, nanotechnology can provide adequate solutions for delivering exogenous NO with the aid of nanoparticles (NPs) to treat ED. The properties of superparamagnetic iron oxide nanoparticles (SPIONs) enable both passive and active delivery of drugs. This prompted us to investigate the efficacy of our newly-developed hydrogel nanoparticles (NO-RPs) for the delivery and sustained release of NO gas to alleviate cardiac failure and inflammation in the heart failure zebrafish model. The hydrogel NO-RPs incorporate SPIONS and NO precursor. The sustainend release of NO in the NO-RPs (4200 s), overcomes the problem of the short half life of NO in vivo which is expected to ameliorate the reduced NO bioavailabilty, and its consequences in endothelial and cardiac dysfunction. Zebrafish embryos were used as the animal model in this study to determine the effect of SPIONs-loaded NO-RPs on the cardiovascular system. Cardiac failure was induced in 24hpf embryos by exposure to aristolochic acid (AA)(0.25, 0.5 μM) for 8 h, followed by the SPIONs-loaded NO-RPs (0.25, 0.5 mg/ml) for 48 h, experimental groups included: control group which is healthy non treated zebrafish embryos, AA injured zebrafish embryos (HF) model,and NO-RP treated HF zebrafish embryos. Survival rate was assessed at 72hpf. Cardiac function was also evaluated by analyzing cardiac parameters including heartbeat, major blood vessels primordial cardinal vein and dorsal aorta (PCV &DA) diameter, blood flow velocity in PCV & DA vessels, cardiac output, and PCV & DA shear stresses. All cardiac parameters were analyzed with the aid of MicroZebraLab blood flow analysis software from Viewpoint. In addition, we studied the molecular effects of the developed NO-RPs on the mRNA expression of selected pro-inflammatory markers: IL-6, and Cox-2. Our findings demonstrated that the NO-RPs improved the survival rate in the heart failure zebrafish model and reversed heart failure by enhancing blood flow perfusion in Zebrafish embryos, significantly. In addition, RT-PCR results showed that the NO-RPs significantly reduced the expression of pro-inflammatory markers (lL-6&COX-2) in the heart failure zebrafish model. Our study confirmed that the developed SPIONs-loaded NO-RPs are effective tool to alleviate cardiac failure and inflammation in the HF zebrafish model., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

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., (© 2022 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.)

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 400μg/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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

The contamination of food and potable water with microorganisms may cause food-borne and water-borne diseases. The common contaminants include Escherichia coli (E. coli), Salmonella sp. etc. The conventional methods for monitoring the water quality for the presence of bacterial contaminants are time-consuming, expensive, and not suitable for rapid on-spot detection in field conditions. In the current study, super paramagnetic iron oxide nanoparticles (SPIONs) were synthesized and conjugated with E. coli specific Aptamer I to detect E. coli cells qualitatively as well as quantitatively. The sludge consisting of E. coli- SPION complex was separated via magnetic separation. The presence of E. coli cells was confirmed with the help of standard techniques and confocal laser scanning microscopy (CLSM) employing Aptamer II conjugated CdTe-MPA quantum dots (QDs). Finally, an ATmega 328P prototype biosensor based on Aptamer II conjugated CdTe MPA QDs exhibited quantitative and qualitative abilities to detect E.coli. This prototype biosensor can even detect low bacterial counts (up to 1 × 10 2 cfu) with the help of a photodiode and plano-convex lens. Further, the prototype biosensor made up of ultraviolet light-emitting diode (UV LED), liquid crystal display (LCD) and ATmega328Pmicrocontroller offers on-spot detection of E.coli in water samples with high resolution and sensitivity. Similarly, this in-house developed prototype biosensor can also be utilized to detect bacterial contamination in food samples., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Textile industries produce a massive amount of wastewater that should be cleaned from toxic substances such as fats, colors and any chemicals used during the production steps. Water-treatment methods should be facile, economic, fast and efficient. Here, we report the synthesis, characterization and application of matrix-dispersed superparamagnetic iron oxide nanoparticles (SPIONs) for the removal of anionic dyes from wastewater released from textile industrial plants. The matrix-dispersed SPIONs were synthesized via a solvothermal method in which a polyethyleneimine (PEI) shell was deposited onto SPIONs in order to add positive charges to their surfaces. TEM images revealed that the size of PEI-coated and uncoated SPIONs is 30-50 and 15-30 nm, respectively. Moreover, TEM images depicted that the as synthesized PEI-coated SPIONs show matrix-dispersed structures. Furthermore, the particle size obtained with DLS measurements was found to be 87.93 and 158.9 nm for uncoated and PEI-coated SPIONs, respectively. Bromophenol blue (BPB) and bromocresol green (BCG), two triphenylmethanes, were used as model anionic dyes. FTIR spectroscopy revealed the interaction between the PEI surface coating and the anionic dyes. The apparent ζ-potential measurements showed that the surface negative charges decreased from -13.5 to -4.03 mV upon coating with PEI. In order to investigate the anionic dyes removal/entrapment efficiency of SPIONs, a new derivative visible spectrophotometric method was developed for the simultaneous quantification of BPB and BCG before and after treatment where the linear ranges were 6.98-27.9 and 6.70-26.8 μg/mL and the recovery values were in the ranges of 98.10-101.7% and 99.55-104.8% for BCG and BPB, respectively. It was found that the uptake/adsorption capacity of PEI-coated SPIONs is ca.15.5 and 11.3 mg/g for BCG and BPB, respectively. The calculated thermodynamic parameters for the adsorption of BCG (ΔH = 37.08 J/mol and ΔS = 120.89 J/mol K) and BPB (ΔH = 181.26 J/mol and ΔS = 596.46 J/mol K) and the negative ΔG values indicate that the adsorption is thermodynamically favored. The adsorption processes were found to follow the pseudo-second-order kinetic model with r 2 values of 0.9982 and 0.9956 for BCG and BPB, respectively., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Oncolytic viruses (OVs) are a class of biotherapeutics that are currently being explored for the treatment of cancer. While showing promise in several pre-clinical and clinical studies, systemic delivery of these anti-cancer agents is hampered by inefficient tumor targeting and a host immune system that is highly evolved to detect and neutralize pathogens. To shield the virus from immune recognition and destruction, the use of cells as delivery vehicles has been explored for the systemic delivery of OVs. Though several types of cell carriers are able to protect OVs during intravenous delivery, many still lack the ability to specifically home to or accumulate within the tumor microenvironment. Overall, OV-based therapeutics could benefit from tumor targeting strategies to maximize tumor-specific delivery and minimize infection of off-target tissues. In the current study, we examine magnetic targeting as a strategy to improve OV infection of tumor cells in vitro. We found that magnetic targeting of magnetically-labeled VSV particles or VSV-infected cell carriers resulted in increased infection and killing of tumor cells. Furthermore, this enhanced infection of target tumor cells was observed even in the presence of virus-specific neutralizing antibodies. Overall, our findings suggest that magnetic targeting strategies can improve the infection of tumor cells and may be a viable strategy to improve the tumor-targeted delivery of oncolytic VSV-based therapeutics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Cancer-Associated Fibroblasts (CAFs) contribute to tumour progression and have received significant attention as a therapeutic target. These cells produce growth factors, cytokines and chemokines, stimulating cancer cell proliferation and inhibiting their apoptosis. Recent advances in drug delivery have demonstrated a significant promise of iron oxide nanoparticles in clinics as theranostic agents, mainly due to their magnetic properties. Here, we designed superparamagnetic iron oxide nanoparticles (SPIONs) to induce apoptosis of human fibroblasts. SPIONs were synthesized via co-precipitation method and coated with sodium citrate (SPION&#95;Cit). We assessed the intracellular uptake of SPIONs by human fibroblast cells, as well as their cytotoxicity and ability to induce thermal effects under the magnetic field. The efficiency and time of nanoparticle internalization were assessed by Prussian Blue staining, flow cytometry and transmission electron microscopy. SPIONs&#95;Cit were detected in the cytoplasm of human fibroblasts 15 min after in vitro exposure, entering into cells mainly via endocytosis. Analyses through Cell Titer Blue assay, AnnexinV-fluorescein isothiocyanate (FITC) and propidium iodide (PI) cellular staining demonstrated that concentrations below 8 × 10 -2  mg/mL of SPIONs&#95;Cit did not alter cell viability of human fibroblast. Furthermore, it was also demonstrated that SPIONs&#95;Cit associated with alternating current magnetic field were able to induce hyperthermia and human fibroblast cell death in vitro, mainly through apoptosis (83.5%), activating caspase 8 (extrinsic apoptotic via) after a short exposure period. Collectively these findings suggest that our nanoplatform is biocompatible and can be used for therapeutic purposes in human biological systems, such as inducing apoptosis of CAFs., Competing Interests: Declaration of competing interest There is no conflict of interest neither competing interest among the Institutions and the researchers involved in this study., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Aims: Evaluation of the anti-diabetic effect of superparamagnetic iron oxide nanoparticles (SPIONs) on Type 2 diabetic rats and compared their effect to metformin treatment., Main Methods: Diabetic rats were treated with different doses of nanoparticles one time per week for 4 weeks. Fasting blood glucose level was determined for studied groups during the experimental period (30 days). At the end of the experiment, oral glucose tolerance test was carried out, serum samples were collected for biochemical assays. Then animals were sacrificed to obtain tissues for assessment of glucose transporters, insulin receptors and insulin signaling proteins., Key Finding: SPIONs treatment normalized fasting blood glucose and lowering insulin level in diabetic rats compared to untreated diabetic rats. SPIONs significantly ameliorate the glucose sensing and the active components of insulin signaling pathway. The anti-diabetic effects of SPIONs may be mediated through its effect on (i) hepatic peroxisome proliferator-activated receptor gamma coactivator 1-alpha content, which induced by SPIONs treatment in a dose-dependent manner, (ii) adipocytokines as SPIONs treated diabetic rats showed significantly higher levels of adiponectin and lower retinol binding protein 4 compared to untreated diabetic rats, (iii) lipid profile as SPIONs treatment significantly corrected the lipid profile in a dose-dependent manner and to a similar extent as metformin or even better., Significance: To our knowledge, this is the first study that explores the anti-diabetic effects of SPIONs on diabetic model., Competing Interests: Declaration of competing interest There are no conflicts to declare., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Multifunctional nanoparticles have emerged as an outstanding candidate for a new generation of biomedical applications, mainly due to their remarkable properties and biocompatibility. Individual reports on multi-metal, semiconducting and superparamagnetic nanoparticles (SPIONs), elucidating on each's unique intrinsic properties, have demonstrated that the biological application of such materials is highly dependent of their size, shape, surface nature and core nature. However, reviews combining nanoparticles with multiple properties, as fluorescence and paramagnetism, as well as, biocompatibility, toxicology and biodegradability are yet seldom. This review highlights the highest output advances, of the last decade, on synthetic procedures for the design of multifunctional magneto-luminescent hybrid nanosystems based on quantum dots, SPIONs and mesoporous silica nanoparticles, as well as, surface modifications and their role for biological applications., (Copyright © 2019 Elsevier B.V. All rights reserved.)

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., (Copyright © 2018 Elsevier Inc. All rights reserved.)

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., (Copyright © 2018. Published by Elsevier B.V.)

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., (Copyright © 2018 Elsevier B.V. All rights reserved.)

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., (Copyright © 2018 Elsevier B.V. All rights reserved.)

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 24h after the injection. Iron was found in the olfactory bulb, temporal lobe, frontal cortex, thalamus and brain stem at 24h 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 24h 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., (Copyright © 2017 Elsevier B.V. All rights reserved.)

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 160nm in diameter, a polydispersity index below 0.2 and a zeta potential of ca. -18mV. Multifunctional nanospheres were monodisperse and stable up to 3months. 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., (Copyright © 2017 Elsevier B.V. All rights reserved.)

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 10nm 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., (Copyright © 2017 Elsevier B.V. All rights reserved.)

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 67nm, 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 (81.77mM -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., (Copyright © 2016 Elsevier B.V. All rights reserved.)

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 24h 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., (Copyright © 2016 Elsevier Inc. All rights reserved.)

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., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2015 Elsevier Inc. All rights reserved.)

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., (Copyright © 2015 Elsevier B.V. All rights reserved.)

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(-1)FemM(-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 © 2014 Elsevier B.V. All rights reserved.)

To treat tumours efficiently and spare normal tissues, targeted drug delivery is a promising alternative to conventional, systemic administered chemotherapy. Drug-carrying magnetic nanoparticles can be concentrated in tumours by external magnetic fields, preventing the nanomaterial from being cleared by metabolic burden before reaching the tumour. Therefore in Magnetic Drug Targeting (MDT) the favoured mode of application is believed to be intra-arterial. Here, we show that a simple yet versatile magnetic carrier-system (hydrodynamic particles diameter <200nm) accumulates the chemotherapeutic drug mitoxantrone efficiently in tumours. With MDT we observed the following drug accumulations relative to the recovery from all investigated tissues: tumour region: 57.2%, liver: 14.4%, kidneys: 15.2%. Systemic intra-venous application revealed different results: tumour region: 0.7%, liver: 14.4 % and kidneys: 77.8%. The therapeutic outcome was demonstrated by complete tumour remissions and a survival probability of 26.7% (P=0.0075). These results are confirming former pilot experiments and implying a milestone towards clinical studies., From the Clinical Editor: This team of investigators studied drug carrying nanoparticles for magnetic drug targeting (MDT), demonstrating the importance of intra-arterial administration resulting in improved clinical outcomes in the studied animal model compared with intra-venous., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Superparamagnetic iron oxide nanoparticles (SPIONs) and oxaliplatin (OHP) were in-situ encapsulated in pectin cross-linked with Ca(2+) forming 100-200 nm sized magnetically functionalized pectin nanocarriers, referred here as MP-OHP nanocarriers. The scanning electron microscopy (SEM) and transmission electron microscopy (TEM) studies revealed formation of spherical nanostructures. The magnetic measurements by vibration sample magnetometer (VSM) revealed high saturation magnetization (M s=45.65 emu/g). The superparamagnetic property of MP-OHP was confirmed from the blocking temperature (T B) determined from field cooled and zero field cooled magnetization, measured by superconducting quantum unit interference device (SQUID) magnetometry. The stability of the aqueous dispersion of MP-OHP nanocarriers was confirmed from its high zeta potential (-30.5 mV). The drug encapsulation efficiency (55.2±4.8% w/w) and the drug loading content (0.10±0.04 wt%) in MP-OHP nanocarriers were determined from corresponding platinum contents in OHP and MP-OHP batches measured by inductively coupled plasma mass spectrometry (ICPMS). These nanocarriers exhibited a sustained release of OHP in phosphate buffer solution maintained at pH 5.5 and 7.4, where the drug release profile satisfied a combination of diffusion and swelling controlled mechanism. The cytotoxicity effect of MP-OHP nanocarriers was studied on MIA-PaCa-2 (pancreas) cancer cell line, where the GI50 values were more than 5 mg/mL and it exhibited 10 folds higher cytoxicity than the equivalent concentration of free drug.