Magnetic Iron Oxide Nanoparticles

MNPs with DNR and Br Tet was by way of mechanical absorp- tion, which meant that the binding of these three agents might not be so compact and that lots of drugs would be released before they reached the target site. To solve this problem, we developed a novel DNR/Br Tet-MNPs formulation, magnetic iron oxide nanoparticles co-loaded with DNR and Br Tet. We used oleic acid-coated iron oxide nanoparticles as drug car- riers, which were further modified by pluronic F-127. DNR and Br Tet were then permeated into the OA shell. It possessed high drug loading capacity and acted as a drug depot for the sustained release of drugs up to 25 days. To study its potential effect on hematologic malignancies, we evaluated the induced apoptosis of self-assembled DNR/Br Tet-MNPs formulation in human leukemia K562/A02 cells and further exploited the potential mechanisms.

Magnetic iron oxide nanoparticles coated with an antibio- fouling “stealth” polysiloxane-containing PEO-b-P γ MPS copolymer have a long blood circulation time with reduced nonspecific uptake by the reticuloendothelial system and macrophages. With covalent conjugation of the antibody against HER2 or ScFvEGFR to PEO-b-P γ MPS-coated IONPs, HER2-targeted or EGFR-targeted IONPs are capable of efficiently targeting breast cancer cells that overexpress HER2 or EGFR, respectively. In contrast, nontargeted IONPs do not show cellular uptake in these cell lines. Furthermore, receptor-specific cell binding and internalization can be effectively inhibited by pretreatment with excess amounts of free anti-HER2 antibody or ScFvEGFR. With the “stealth” properties demonstrated in this study, these IONPs facili- tate effective targeting of cancer cells. Such antibiofouling polymer-coated magnetic nanoparticles with their biomarker- targeting ability are promising candidates for the develop- ment of molecular imaging probes and image-assisted drug delivery carriers.

As a competitive alternative, the sonochemical method has been extensively used to generate novel materials with unusual properties. The chemical effects of ultrasound arise from acoustic cavitation, that is, the formation, growth, and implosive collapse of bubbles in liquid. The implosive collapse of the bubble generates a localized hotspot through adiabatic compression or shock wave formation within the gas phase of the collapsing bubble. The condi- tions formed in these hotspots have been experimentally determined, with transient temperatures of 5000 K, pres- sures of 1800 atm, and cooling rates in excess of 10 10 K/s [36]. These extreme conditions were beneficial to form the new phase, and have a shear effect for agglomeration, which is prone to prepare the highly monodispersive NPs. This method has been applied for the synthesis of various nanocomposites, and its versatility has been successfully demonstrated in iron oxide NPs preparation [37]. For instance, magnetite NPs can be simply synthesized by sonication of iron(II)acetate in water under an argon atmosphere. Vijayakumar et al. [38] reported a sonochem- ical synthetic route for preparing the pure nanometer-size

completion of the incubation period, the fresh medium containing blank nanoparticles or drug encapsulated nano- particles were added to each well. Over a period of time, 10 µL of the (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenylte- trazolium bromide) MTT solution (5 mg mL − 1 ) was added to each well, and then plates were further incubated for 4 h. Then, 100 µL of a formazan lysis solution (10% SDS in 0.1N HCl) was added to each well. The absorbance was measured at a wavelength of 570 nm using a microplate reader (BIO-RAD).

magnetic nanoparticles, as a new kind of nanometer-sized materials are attractive because they can exhibit an array of novel and specified properties such as large surface area, potential for high specificity, high reactivity, catalytic potential, and absence of internal diffusion resistance, which are promising to develop new or improve existing technologies in wastewater treatment. These particles are superparamagnetic, which means that they are attracted to a magnetic field, but retain no residual magnetism after the field is removed. Therefore, suspended are superparamagnetic particles adhered to the target can be removed very quickly from a matrix using a magnetic field, but they do not agglomerate after removal of the field [6-10]. Present work introduces an efficient removal of Hg +2 ion from wastewater using modified magnetic iron oxide nanoparticles with polyethylene glycol (PEG) that can from strong complex with Hg (II) ion. The major advantages of technology are its effectiveness in reducing the concentration of heavy metal ions such as Hg 2+, avoid the generation of secondary waste, produced no contaminants, has the capability of treating large amount of wastewater within a short time, good selectivity and the adsorption materials employed in this method can be recycled and used easily on an industrial scale.

Medarova et al. synthesized a breast tu- mor-targeted nanodrug designed to specifically shut- tle siRNA to human breast cancer while simultane- ously allowing for the noninvasive monitoring of the siRNA delivery process [71]. The nanodrug consisted of SPIONs for MRI monitoring, Cy5.5 fluorescence dye for near-infrared (IR) optical imaging, and siRNA to target the tumor-specific antiapoptotic gene BIRC5. Magnetic iron oxide nanoparticles are extensively used as multimodal imaging probes in combination with optical fluorescence dyes to obtain the benefits of optical imaging, such as rapid screening and high sensitivity. Because tumor-associated underglycosyl- ated mucin-1 (uMUC-1) antigen is overexpressed in >90% of breast cancers and in >50% of all cancers in humans [72], researchers have decorated nanodrugs with uMUC-1-targeting EPPT synthetic peptides for selective tumor targeting. As shown in Figure 3A, amine-functionalized superparamagnetic iron oxide nanoparticles with a cross-linked dextran coating (MN) have been prepared, and a Cy5.5 dye was con- jugated to the surface of nanoparticles to produce MN-Cy5.5. Subsequently, thiol-modified, FITC-labeled EPPT peptides and siRNA were coupled to MN-Cy5.5 via a heterofunctional cross-linker, N-succinimidyl 3-(2-pyridyldithio) propionate (SPDP). The resulting therapeutic and diagnostic nanodrug (MN-EPPT-siBIRC5) exhibited superpara- magnetic and fluorescence properties. After intrave- nous injection of the nanodrugs into mice with BT-20 breast tumors, the tumors were clearly imaged, as verified simultaneously by T2 MRI and near-IR opti- cal imaging (Figure 3B). Systemic administration of the nanodrug once a week over 2 weeks induced con- siderable levels of necrosis and apoptosis in the tu- mors as a result of the siBIRC5-mediated inhibition of the antiapoptotic survivin protooncogene, translating into a significant decrease in tumor growth rate (Fig- ure 3C). This tumor-targeted, imaging-capable nanodrug highlights the potential of MRI-guided tumor treatment, which can be used to quantify changes in the tumor volume over the treatment schedule as well as to guide selection of an optimal treatment time course.

A feasible and fast method for Adult Hemoglobin (A-Hb) and Fetal Hemoglobin (F-Hb) study was developed by immobilization of Hb on gold-coated magnetic iron oxide nanoparticles (GMNPs).The prepared GMNPs composite nanoparticles with 60 nm diameter were used as a carrier for the immobilization of Hb. The A-Hb and F-Hb were physically attached to the GMNPs nanoparticles. The direct electroche- mistry of F-Hb and A-Hb showed a quasi-reversible cyclic voltammogram corres- ponding to the Heme group with a formal potential of 314 and -334 mV in 0.1M PBS (pH 6.2), respectively. The apparent charge transfer rate constant (ks) and transfer coefficient (α) for electron transfer between the electrode surface and pro- tein were calculated as 0.29/s and 0.1 for F-Hb and 0.21/s and 0.47 for A-Hb. The linear concentration rangesare17.3–225 and 7.4-53 mM for F-H band A-Hb biosen- sors for H 2 O 2 detection. The lifetime of biosensor is more than 2 weeks.

Abstract: The present work aims to demonstrate that colloidal dispersions of magnetic iron oxide nanoparticles stabilized with dextran macromolecules placed in an alternating magnetic field can not only produce heat, but also that these particles could be used in vivo for local and non-invasive deposition of a thermal dose sufficient to trigger thermo-induced gene expression. Iron oxide nanoparticles were first characterized in vitro on a bio-inspired setup, and then they were assayed in vivo using a transgenic mouse strain expressing the luciferase reporter gene under transcriptional control of a thermosensitive promoter. Iron oxide nanoparticles dispersions were applied topically on the mouse skin or injected sub-cutaneously with Matrigel™ to generate so called pseudo tumors. Temperature was monitored continuously with a feedback loop to control the power of the magnetic field generator and to avoid overheating. Thermo-induced luciferase expression was followed by bioluminescence imaging 6 hours after heating. We showed that dextran-coated magnetic iron oxide nanoparticles dispersions were able to induce in vivo mild hyperthermia compatible with thermo-induced gene expression in surrounding tissues and without impairing cell viability. These data open new therapeutic perspectives for using mild magnetic hyperthermia as non-invasive modulation of tumor microenvironment by local thermo-induced gene expression or drug release.

Magnetic iron oxide nanoparticles have been investigated for their magnetic capacities, very promising for mag- netic resonance imaging (MRI) contrast enhancement [63], and hyperthermia [64]. A large number of func- tional groups to target tumors can be attached to their surface, such as antibodies, peptides, or small molecules for diagnostic imaging or drug therapy [65,66]. Moreover surface modifications in these nanoparticles have been shown to render them biocompatibles with long blood retention times and low toxicity [1]. Among the mole- cules used for coating magnetic nanoparticles to increase their stability and half-life circulation are dextran, poly- saccharides, PEG and polyethylene oxide [8]. Superpara- magnetic iron oxide nanoparticles (SPIONs) are com- posed of an iron oxide core of about 5 - 10 nm, and a sur- rounding layer of stabilising macromolecules, resulting in particle diameters of 30 - 80 nm [67]. The superpara- magnetic property of iron oxide is due to a magnetic moment in the presence of an external magnetic field. The most widely used method for synthesis of SPIONs is alkaline co-precipitation of Fe(OH) 2 and Fe(OH) 3 sus-

nanoparticles were produced at lower pH (pH 5). Lunge et al. [93] have synthesized magnetic iron oxide nanoparticles of 2–25 nm with cuboid/pyramid structure using tea waste template. They exhibited high adsorption capacity for arsenic. It showed very low cost (Rs. 136 per kg). These nanoparticles may be reused up to 5 cycles and regenerated using NaOH. The estimated cost of As(III) removal from water was estimated to be negli- gible. Leaf extracts of 26 plants were used for the pro- duction of nanoscale zero-valent iron particles [37]. The optimum temperature (80 °C) was noted; however, for the extraction time and leaf mass, solvent volume ratio was varied according to the leaf type. Thakur and Karak [32] used banana peel ash extract to synthesize iron oxide nanoparticles; and aqueous extract of Colocasia esculenta leaves was used to reduce graphene oxide. Iron oxide formation was validated by XRD (peaks at 30.15, 36.2, 43.32, 53.89, and 29) and FTIR (stretching Fe–O) (Fig. 1a, b). In this study, the nanohybrids exhibited a good reusability with insignificant decrease in efficiency even after the third cycle [32].

The present manuscript describes the synthesis and character- ization of novel magnetic fibrin scaffolds for cell engineering prepared by the interaction of thrombin-conjugated magnetic iron oxide nanoparticles with fibrinogen. In addition, this manuscript shows that the conjugation of bFGF, either cova- lently or physically, to the γ -Fe 2 O 3 nanoparticles significantly enhances the migration, growth, and differentiation of NOM cells seeded within the fibrin scaffolds compared to the same concentration, or even five times higher, of the free bFGF. In future work we plan to extend these studies to growth factors other than bFGF, eg, GDNF and NGF. In addition, we plan to use the optimal magnetic fibrin scaffolds containing the growing NOM cells and the growth factors conjugated nano- particles as composite implants for the treatment of spinal cord transacted rats. Since these scaffolds have magnetic proper- ties, we intend to monitor the healing process by MRI.

On the other hand, about 1–4 months were necessary, respectively, to completely clear 10 (Figure S1) or 50 mg/kg (yellow rectangles in Figure 3) of cat-USPIOs from the liver, the organ responsible for detoxification of the organism through hepatocytes, that are known to accumulate iron(III) as ferritin or hemosiderin. Even in this unfavorable case, the amount of cat-USPIOs accumulated in the liver after injec- tion of 10 mg/kg started to show decreasing negative contrast after 2 weeks. However, 60 days were necessary to observe a similar effect in the male Wistar rats that received the highest dose. Before those periods, the concentration of cat-USPIOs was too high such that variations in the negative contrast level could not be noticed. All rats used in the experiments survived and showed no change in their behavior indicating no significant toxicity, good tolerance, and total clearance of magnetite nanoparticles as a function of time even at the very high dose of 50 mg/kg. Proportionally, a 70 kg human adult would receive 3.5 g of cat-USPIOs, a dose much higher than that needed in typical MRI diagnoses (typically 0.16–0.24 mg of Fe 3 O 4 , ie, 10–15 µ mol Fe/kg body weight). However, the dosage of 10 mg/kg is commonly used in MRI studies with rats using SPIOs as contrast agents. 8

Monolayer polymer coating and organic ligand coat- ing have successfully been converted hydrophobic nature into water soluble and biocompatible. Other than this, iron NPs coated with other biomolecules have enhanced their biocompatibility gaining them approval by authorities such as the US Food and Drug Administration. Therefore, the iron NPs are routinely used in the fields of MRI, target- specific drug delivery, gene therapy, cancer treatments, in vitro diagnostics, and many more. Although magnetic NPs exhibit many distinctive properties, more toxicologi- cal research is needed and the criteria to evaluate toxicity

Osmotic disruption of the BBB has been extensively studied and is a clinically proven method for enhancing the brain delivery of poorly permeable compounds. As expected, treatment of the cells with 1.4 M mannitol significantly enhanced FDX-70,000 permeability compared with the intact BBB model (Figure 3A and C). However, it should be noted that the apparent permeability coefficients of FDX and both IONP formulations were higher in blank membrane than the disrupted BBB model, suggesting that some cellular resis- tance to passage of solutes remained even in a disrupted state (Table 1). Under high osmotic conditions, permeability of the positively charged AmS-IONPs was found to be less than 5% in the absence of a magnetic field, and no significant change was observed with the application of a magnetic field (Figure 3B). This was in contrast to the negatively charged EDT-IONPs that displayed a 30% flux after 24 hours (Figure 3D) in the mannitol treatment group. In addition, the application of an external magnetic field further enhanced the permeability of EDT-IONPs in the mannitol-treated mono- layers, which significantly exceeded the flux observed with the FDX permeability marker at the 24-hour point (Figure 3C

The particle size and morphology of the coated MNPs was determined by transmission electronic microscopy (TEM, JEOL, JEM-200EX). Powder X-ray diffraction (XRD, Rigaku, D/Max-RA, k = 1.5405 9 10 -10 m, CuK) was used to determine the crystal structure of MNPs. Surface charge measurements were performed with a zeta potential analyzer (BECKMAN, Delsa 440SX). The magnetic measurements were carried out with a vibrating sample magnetometer (VSM, Lakeshore 7407). Fourier transform infrared (FTIR) spectroscopy measurements were per- formed on a Bruker Fourier transform spectrometer model VECTOR22 using KBr pressed discs.

Introduction: Nowadays, nanoparticles (NPs) have attracted much attention in biomedical imaging due to their unique magnetic and optical characteristics. Superparamagnetic iron oxide nanoparticles (SPIONs) are the prosperous group of NPs with the capability to apply as magnetic resonance imaging (MRI) contrast agents. Radiolabeling of targeted SPIONs with positron emitters can develop dual positron emission tomography (PET)/MRI agents to achieve better diagnosis of clinical conditions.

Abstract: The objective of this study was to investigate the anticancer efficacy of dimercaptosuccinic acid-modified iron oxide magnetic nanoparticles coloaded with anti-CD22 antibodies and doxorubicin (anti-CD22-MNPs-DOX) on non-Hodgkin’s lymphoma cells. The physical properties of anti-CD22-MNPs-DOX were studied and its antitumor effect on Raji cells in vitro was evaluated using the Cell Counting Kit-8 assay. Furthermore, cell apoptosis and intracellular accumulation of doxorubicin were determined by flow cytometry. The results revealed that anti-CD22-MNPs-DOX inhibited the proliferation of Raji cells, significantly increased the uptake of doxorubicin, and induced apoptosis. Therefore, it was concluded that a coloaded antibody and chemo therapeutic drug with magnetic nanoparticles might be an efficient targeted treatment strategy for non-Hodgkin’s lymphoma.

In all magnetofection experiments so far, iron oxide nanoparticles were used. These particles are "superparamagnetic", meaning that they are strongly attracted to a magnetic field but they do not retain residual magnetism after the field is removed. Therefore they can not agglomerate (like ferromagnetic particles) after removal of the magnetic field. Further, Weissleder et al. found that iron oxide particles used as contrast agents in magnetic resonance imaging (MRI) are fully biocompatible (Weissleder et al., 1989). After intravenous application in rats, the particles were cleared by macrophages in liver and spleen, the iron oxides were degraded in lysosomes via hydrolytic enzymes, and the resulting elemental iron was integrated into the natural iron metabolism (e.g. incorporation into hemoglobin). Additionally, Weissleder and coworkers showed that in rats and beagle dogs a relatively high dose of 167 mg iron/kg body mass still had no toxic effects on the liver or other organs and they mentioned that for clinical MRI a dose of approximately 1 mg iron/kg is proposed. Thus, the 76.9 µg iron oxide particles/kg applied intravenously in pigs for magnetic nucleic acid targeting experiments (3.4.1) can be assumed to be totally safe. Despite the advanced magnetic properties and the biocompatibility of iron oxides, for improvement of magnetic nucleic acid targeting materials with even higher magnetic susceptibility (see χ in the formula above) would be desirable. For example, the ferromagnetic material elementary iron has a higher magnetic susceptibility and a higher saturation magnetization as iron oxide (magnetite) and composite microparticles made from elementary iron and activated carbon were already used for magnetic drug targeting with chemotherapeutic agents in human clinical trials (Johnson et al., 2002; Rudge et al., 2001). Therefore in future it might be interesting to work on the efficient and functional binding of nucleic acids to elementary iron particles and to test these associates in magnetofection.

options to be employed as protective coatings on iron oxide nanoparticles thanks to their stability under aqueous conditions and ease of synthesis [20]. Trialkoxysilanes , bifunctional molecules ,entail a trialkoxy group that they are granted to modify the surface of nanoparticles . (3-Aminopropyl) triethoxysilane is intended to be done through the grafting of aminopropylsilane groups (–O) 3 Si– (CH 2 ) 3 –NH 2 via formation of covalent bonds which are bound to the particle surface and makes basic surface. Following prior step, it would be regarded as nanocarrier attracting acidic drugs resulted in an ionic interaction 21, 22 . Modified magnetic

The magnetic properties of nanomaterials depend on their crystal structure and average particle size. Hence, in order to investigate the effect of the iron oxide distribution on the magnetic behavior of the ferrite nanoparticles, their magnetization profiles (in terms of the magnetic field and annealing temperature) were obtained. Figure 3 (a-d) show the hysteresis curves for the nanoparticles at 5 and 300 K. As expected, at 5 K, the samples showed higher magnetic saturation than at 300 K (Table 2). This behavior is characteristic of ferrimagnetic materials (Cai, 2007). At 300 K, the samples exhibited a superparamagnetic behavior because of the formation of very short magnetic domains (Gavilán, 2017). To determine the veracity of the superparamagnetic state of the nanoparticles, a mathematical adjustment of the hysteresis curve was carried out using the Langevin function assuming a set of polydisperse nanoparticles each with a magnetic moment (μ) described by Eq. 2: