Dextran-coated Iron Oxide Nanoparticles Research Articles

MRI-Tracking of Dental Pulp Stem Cells In Vitro and In Vivo Using Dextran-Coated Superparamagnetic Iron Oxide Nanoparticles.

The aim of this study was to track dental pulp stem cells (DPSCs) labeled with dextran-coated superparamagnetic iron oxide nanoparticles (SPIONs) using magnetic resonance imaging (MRI). Dental pulp was isolated from male Sprague Dawley rats and cultured in Dulbecco’s modified Eagle’s medium F12 (DMEM-F12) and 10% fetal bovine serum. Effects of SPIONs on morphology, viability, apoptosis, stemness, and osteogenic and adipogenic differentiation of DPSCs were assessed. Prussian blue staining and MRI were conducted to determine in vitro efficiency of SPIONs uptake by the cells. Both non-labeled and labeled DPSCs were adherent to culture plates and showed spindle-shape morphologies, respectively. They were positive for osteogenic and adipogenic induction and expression of cluster of differentiation (CD) 73 and CD90 biomarkers, but negative for expression of CD34 and CD45 biomarkers. The SPIONs were non-toxic and did not induce apoptosis in doses less than 25 mg/mL. Internalization of the SPIONs within the DPSCs was confirmed by Prussian blue staining and MRI. Our findings revealed that the MRI-based method could successfully monitor DPSCs labeled with dextran-coated SPIONs without any significant effect on osteogenic and adipogenic differentiation, viability, and stemness of DPSCs. We provided the in vitro evidence supporting the feasibility of an MRI-based method to monitor DPSCs labeled with SPIONs without any significant reduction in viability, proliferation, and differentiation properties of labeled cells, showing that internalization of SPIONs within DPSCs were not toxic at doses less than 25 mg/mL. In general, the SPION labeling does not seem to impair cell survival or differentiation. SPIONs are biocompatible, easily available, and cost effective, opening a new avenue in stem cell labeling in regenerative medicine.

P11.42 Magnetic targeting of the granzyme B functionalized nanoparticles for therapy of glioblastoma

Abstract BACKGROUND Magnetic drug targeting by employing external magnetic fields represents a promising approach for treatment of glioblastoma. To increase the anti-tumor therapeutic effect magnetic nanocarriers could be functionalized with tumor-targeting bioligands such as granzyme B (GrB). The serine protease GrB that is produced as an effector molecule by activated NK and T cells can induce specific tumor cell apoptosis. MATERIAL AND METHODS The targeting potential of the dextran-coated superparamagnetic iron oxide nanoparticles conjugated with GrB (GrB-SPIONs) was assessed in glioblastoma cells (U87, C6, GL261) by flow cytometry, confocal and electron microscopies. Magnetic field strength (320 mT) in the models of U87 glioblastoma in NMRI nu/nu mice and C6 glioma in Wistar rats was achieved by employing NdFeB cylindrical ferromagnet. The irradiation of the implanted tumors was performed using the CT-image guided Small Animal Radiation Research Platform (SARRP). Accumulation of the nanoparticles was assessed in paraffine-embedded specimens employing Prussian blues staining. Sections were additionally analyzed by IHC for apoptosis (caspase 3). RESULTS Synthesized GrB-SPIONs incorporated into the cytoplasm of tumor cells via the endolysosomal pathway and induced apoptosis in a dose-dependent manner. Intravenous injection of GrB-SPIONs resulted in the glioma-specific retention of the nanoparticles as was shown by high-field (11 T) magnetic resonance imaging and biodistribution studies (NLR-M2 measurements). Magnetic targeting of the nanoparticles in vivo drastically enhanced the accumulation of nanoparticles to the location of the magnet. Thus the local retention of nanoparticles was 12.3-fold higher as compared to application of GrB-SPIONs without external magnetic field. The presence of granzyme B on SPIONs has been shown to promote tumor cells death (IHC staining for caspase 3) and significantly increased overall survival. A combination of nanoparticle treatment with a single radiation dose (10 Gy) significantly prolonged the survival of rats as compared to animals treated only with magnetic targeting of GrB-SPIONs or radiotherapy alone (P<0.001). CONCLUSION Single-agent therapy with GrB-SPIONs demonstrated an impressive increase in overall survival of tumor-bearing animals. Combinatorial regimen employing magnetic targeting and stereotactic radiotherapy further enhanced the therapeutic potential of magnetic conjugates.

The antitoxic effects of quercetin and quercetin-conjugated iron oxide nanoparticles (QNPs) against H2O2-induced toxicity in PC12 cells.

BackgroundWe recently showed that quercetin-conjugated iron oxide nanoparticles (QNPs) promoted the bioavailability of quercetin (Qu) in the brain of rats and improved the learning and memory of diabetic rats. In this study, we characterized the modifications in the antitoxic effects of Qu after conjugation.Materials and methodsWe conjugated Qu to dextran-coated iron oxide nanoparticles (DNPs) and characterized DNPs and QNPs using FTIR, XRD, DLS, Fe-SEM, and EDX analyzes. The antiradical properties of Qu, DNPs, and QNPs were compared by 2, 2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity assay. Catalase-like activities of DNPs and QNPs were estimated using catalase activity assay kit, and the antitoxic effects of Qu and QNPs were evaluated with spectrophotometry, MTT assay, flow cytometry, and real-time q-PCR.ResultsQu had a stronger anti-radical activity than DNPs and its activity decreased after being conjugated to DNPs. The catalase-like activity of DNPs remained intact after conjugation. DNPs had less toxicity on PC12 cells viabilities as compared to free Qu, and the conjugation of Qu with DNPs attenuated its cytotoxicity. Furthermore, MTT assay results indicated 24 h pretreatment with Qu had more protective effects than QNPs against H2O2-induced cytotoxicity, while Qu and QNPs had the same effects for 48 and 72 h incubation. Although the total antioxidant capacity of Qu was attenuated after conjugation, the results of flow cytometry and real-time q-PCR confirmed that 24 h pretreatment with the low concentrations of Qu and QNPs had the similar antioxidant, anti-inflammatory, and anti-apoptotic effects against the cytotoxicity of H2O2.ConclusionQu and QNPs showed the similar protective activities against H2O2-induced toxicity in PC12 cells. Given the fact that QNPs have magnetic properties, they may serve as suitable carriers to be used in neural research and treatment.

Dextran-coated iron oxide nanoparticle for delivery of miR-29a to breast cancer cell line

In the last years, miRNAs have been associated with molecular pathways of cancer and other diseases. The change of expression level of miRNA has an inhibitory role in tumorigenesis. Nevertheless, the poor bioavailability of miRNA due to the rapid enzymatic degradation is a critical handicap in cancer therapy. In this study, we designed dextran-coated iron oxide-based nanoparticle for the delivery of miR-29a to breast cancer cells and analyzed its therapeutic efficacy in vitro. Results indicated that the presence of dextran-coated magnetic nanoparticles, loaded with miR29a, enhanced the selective delivery of miR-29a. Further, miR-29a complex nanoparticles caused down-regulation of anti-apoptotic genes. These results pave the way for further investigations into the possible use of miR-29a complex magnetic nanoparticles for breast cancer therapy.

UMUC1-Targeting Magnetic Resonance Imaging of Therapeutic Response in an Orthotropic Mouse Model of Colon Cancer.

Noninvasive assessment of chemotherapeutic response in colon cancer would tremendously aid in therapeutic intervention of cancer patients and improve outcomes. The aim of the study was to evaluate the feasibility of a noninvasive assessment of chemotherapeutic response by magnetic resonance imaging utilizing underglycosylated mucin 1 (uMUC1) tumor antigen as a biomarker of therapeutic response in a colon cancer mouse model. The study was performed by applying molecular imaging approach based on targeting uMUC1 with specific dual-modality imaging probe (MN-EPPT). The probe consisted of dextran-coated iron oxide nanoparticles conjugated to the near infrared fluorescent dye Cy5.5 and to a uMUC1-specific peptide (EPPT) and was used for magnetic resonance imaging (MRI) and fluorescence optical imaging. An orthotopic murine model of colon cancer expressing human uMUC1 peptide (MC38 MUC1) was created along with the control model devoid of the antigen (MC38 neo). Animals received chemotherapy with 5-fluorouracil (5-FU) followed by MN-EPPT-enhanced MR and optical imaging. In vivo imaging of animals with uMUC1 expressing tumors after 5-FU therapy showed that the average deltaT2 was reduced by 7.27ms (p = 0.045) compared with animals in control groups indicating lower accumulation of MN-EPPT caused by uMUC1 downregulation. In vivo optical imaging, biodistribution, and fluorescence microscopy confirmed the MRI findings. Interestingly, we found that the group of animals that did not respond to chemotherapy ("progressive disease" per RECIST) showed higher accumulation of MN-EPPT compared to the group of responders ("stable disease") consistent with proliferating tumor cells and increased antigen availability. We believe that in application to over 50% of human cancers expressing uMUC1, our results could provide insight into overall assessment of therapeutic response based on its expression as defined by non-invasive MN-EPPT-enhanced MRI.

Dextran-Coated Iron Oxide Nanoparticles as Biomimetic Catalysts for Localized and pH-Activated Biofilm Disruption.

Biofilms are surface-attached bacterial communities embedded within an extracellular matrix that create localized and protected microenvironments. Acidogenic oral biofilms can demineralize the enamel-apatite on teeth, causing dental caries (tooth decay). Current antimicrobials have low efficacy and do not target the protective matrix and acidic pH within the biofilm. Recently, catalytic nanoparticles were shown to disrupt biofilms but lacked a stabilizing coating required for clinical applications. Here, we report dextran-coated iron oxide nanoparticles termed nanozymes (Dex-NZM) that display strong catalytic (peroxidase-like) activity at acidic pH values, target biofilms with high specificity, and prevent severe caries without impacting surrounding oral tissues in vivo. Nanoparticle formulations were synthesized with dextran coatings (molecular weights from 1.5 to 40 kDa were used), and their catalytic performance and bioactivity were assessed. We found that 10 kDa dextran coating provided maximal catalytic activity, biofilm uptake, and antibiofilm properties. Mechanistic studies indicated that iron oxide cores are the source of catalytic activity, whereas dextran on the nanoparticle surface provided stability without blocking catalysis. Dextran-coating facilitated NZM incorporation into exopolysaccharides (EPS) structure and binding within biofilms, which activated hydrogen peroxide (H2O2) for localized bacterial killing and EPS-matrix breakdown. Surprisingly, dextran coating enhanced selectivity toward biofilms while avoiding binding to gingival cells. Furthermore, Dex-NZM/H2O2 treatment significantly reduced the onset and severity of caries lesions (vs control or either Dex-NZM or H2O2 alone) without adverse effects on gingival tissues or oral microbiota diversity in vivo. Therefore, dextran-coated nanozymes have potential as an alternative treatment to control tooth decay and possibly other biofilm-associated diseases.

Application of dextran-coated iron oxide nanoparticles in enhancing the radiosensitivity of cancerous cells in radiotherapy with high-energy electron beams.

Nowadays, cancer is one of the most important causes of morbidity and mortality in the world. The ideal aim of radiotherapy is delivering a lethal radiation dose to tumor cells while minimizing radiation exposure to healthy tissues around the tumor. One way to increase the dose in the tumor cells is the use of high-atomic number nanoparticles as radiosensitizer agents in these cells. The aim of this in vitro study was investigating the radiosensitization enhancement potential of the dextran-coated iron oxide nanoparticles (IONPs) on HeLa and MCF-7 cell lines in irradiations with high-energy electron beams. In this in vitro study, the cytotoxicity level of dextran-coated IONPs at different concentrations (10, 40, and 80 μg/ml) was assessed on HeLa and MCF-7 cell lines. To evaluate the radiosensitivity effect, the nanoparticles were incubated with the cells at different concentrations for 24 h and afterward irradiated with different doses (0, 2, 4, 6, and 8 Gy) of 6 and 12 MeV electron beams. The cells survival fractions were obtained by the methylthiazoletetrazolium assay. Toxicity results of the nanoparticles at 10 and 40 μg/ml concentrations showed no significant cytotoxicity effect. The cells survival rates in groups receiving radiation in the absence and presence of IONPs showed a significant difference. The radiosensitivity enhancement induced by the nanoparticles in MCF-7 cell line was more than it in HeLa cell line. The average of radiosensitization enhancement factor at 10, 40, and 80 μg/ml concentrations and under 6 MeV irradiations obtained as 1.13, 1.19, 1.25, and 1.26, 1.28, 1.29 for HeLa, and MCF-7 cells, respectively. When 12 MeV electron beams were carried out, the values of 1.17, 1.26, 1.32, and 1.29, 1.32, 1.35 were obtained for the cells at the mentioned concentrations, respectively. Furthermore, the significant differences were observed in radiosensitization enhancement between 6 and 12 MeV electron beams irradiations. Use of dextran-coated IONPs can increase radiosensitivity and consequently at a given absorbed dose more cell killing will occur in cancerous cells. In other words, these nanoparticles can improve the efficiency of electron therapy.

P6481Novel dextran-coated ultrasmall superparamagnetic iron oxide nanoparticles (USPIOs) - a safe contrast agent for magnetic resonance imaging of atherosclerosis

P6481Novel dextran-coated ultrasmall superparamagnetic iron oxide nanoparticles (USPIOs) - a safe contrast agent for magnetic resonance imaging of atherosclerosis

Hepatotoxicity and nephrotoxicity of quercetin, iron oxide nanoparticles, and quercetin conjugated with nanoparticles in rats

The pharmaceutical use of quercetin is limited due to the problems such as low solubility, bioavailability, permeability, and instability. High doses of quercetin show toxic effects in clinical and experimental studies. Therefore, a method is needed to overcome these problems without the use of toxic doses. Iron oxide nanoparticles can be used as a drug delivery system. Biocompatible polymers such as dextran are used to cover nanoparticles to increase the stability of nanoparticles. Besides their beneficial effects, nanoparticles can cause toxicity, oxidative stress, and cellular dysfunction. The aim of the present study was to investigate the hepatotoxicity and nephrotoxicity of dextran-coated iron oxide nanoparticles (IONPs) and quercetin conjugated with IONPs (QNPs). This study was conducted for 1 week in eight groups of Wistar male rats including control, sham, quercetin (at doses of 50 and 100 mg/kg), dextran-coated IONPs (at doses of 50 and 100 mg/kg), and QNPs (at doses of 50 and 100 mg/kg). Rats were euthanized, and their liver and kidney tissues were evaluated for the changes in oxidative stress indices and important biochemical enzyme activities. Hepatic and renal AST, ALT, ALP, GGT, and LDH activities were not significantly different between control group and other groups. Hepatic TAC and GSH levels and CAT activity significantly increased, and MDA level significantly decreased in rats injected with 100 mg/kg quercetin compared to the control group. IONPs of 100 mg/kg induced a significant decrease in hepatic GSH level and CAT activity and a significant increase in hepatic MDA. Hepatic TAC, GSH and MDA levels, and CAT activity were not significantly different between QNP groups and the control group. Renal CAT activity showed a significant increase in 100 mg/kg quercetin group and a significant decrease in 100 mg/kg IONP group compared to the control group. However, renal TAC, GSH, and MDA levels were not significantly different among groups. Dextran-coated IONPs of 100 mg/kg caused oxidative damage in the hepatic tissue, but QNPs did not cause hepatic and renal oxidative injury.

In Vivo MRI of Functionalized Iron Oxide Nanoparticles for Brain Inflammation.

Microglia are intrinsic components of the brain immune system and are activated in many central nervous system disorders. The ability to noninvasively image these cells would provide valuable information for both research and clinical applications. Today, most imaging probes for activated microglia are mainly designed for positron emission tomography (PET) and target translocator proteins that also reside on other cerebral cells. The PET images obtained are not specific for microglia-driven inflammation. Here, we describe a potential PET/MRI multimodal imaging probe that selectively targets the scavenger receptor class A (SR-A) expressed on activated microglia. These sulfated dextran-coated iron oxide (SDIO) nanoparticles are avidly taken up by microglia and appear to be nontoxic when administered intravenously in a mouse model. Intravenous administration of this SDIO demonstrated visualization by T2∗-weighted MRI of microglia activated by intracerebral administration of tumor necrosis factor alpha (TNF-α). The contrast was significantly enhanced by SDIO, whereas there was little to no contrast change in animals treated with nontargeted nanoparticles or untreated controls. Thus, SR-A targeting represents a promising strategy to image activated microglia in the brain.

Molecular Rearrangement of Glucans from Natural Starch To Form Size-Controlled Functional Magnetic Polymer Beads.

Herein, we report a fairly simple and environmentally friendly approach for the fabrication of starch-based magnetic polymer beads (SMPBs) with uniform shape and size through spontaneous rearrangement of short-chain glucan (SCG) produced by enzymatic debranching of waxy maize starch. The paramagnetic materials, dextran-coated iron oxide nanoparticles (Dex@IONPs), were readily incorporated into the starch microstructure and rendered a superparamagnetic property to the SMPBs. The morphology and size of resulting SMPBs turned out to be modulated by Dex@IONPs in a concentration-dependent manner, of which Dex@IONPs was assumed to be acting as a seed inducing the epitaxial crystallization of SCG and further transforming it into homogeneous microparticles. The surface of SMPBs was readily functionalized with an antibody through a one-step reaction using a linker protein. The immuno-SMPBs showed great capture efficiency (>90%) for target bacteria. The colloidal stability and favorable surface environment for biomolecules are believed to be responsible for the high capture efficiency and specificity of the SMPBs. Furthermore, the captured bacteria along with antibody and linker protein were effectively eluted from the surface of SMPBs by adding free maltose, making this new material suitable for various chromatographic applications.

On the use of superparamagnetic hydroxyapatite nanoparticles as an agent for magnetic and nuclear in vivo imaging

The identification of alternative biocompatible magnetic NPs for advanced clinical application is becoming an important need due to raising concerns about iron accumulation in soft issues associated to the administration of superparamagnetic iron oxide nanoparticles (NPs). Here, we report on the performance of previously synthetized iron-doped hydroxyapatite (FeHA) NPs as contrast agent for magnetic resonance imaging (MRI). The MRI contrast abilities of FeHA and Endorem® (dextran coated iron oxide NPs) were assessed by 1H nuclear magnetic resonance relaxometry and their performance in healthy mice was monitored by a 7 Tesla scanner. FeHA applied a higher contrast enhancement, and had a longer endurance in the liver with respect to Endorem® at iron equality. Additionally, a proof of concept of FeHA use as scintigraphy imaging agent for positron emission tomography (PET) and single photon emission computed tomography (SPECT) was given labeling FeHA with 99mTc-MDP by a straightforward surface functionalization process. Scintigraphy/x-ray fused imaging and ex vivo studies confirmed its dominant accumulation in the liver, and secondarily in other organs of the mononuclear phagocyte system. FeHA efficiency as MRI-T2 and PET-SPECT imaging agent combined to its already reported intrinsic biocompatibility qualifies it as a promising material for innovative nanomedical applications. Statement of SignificanceThe ability of iron-doped hydroxyapatite nanoaprticles (FeHA) to work in vivo as imaging agents for magnetic resonance (MR) and nuclear imaging is demonstrated. FeHA applied an higher MR contrast in the liver, spleen and kidneys of mice with respect to Endorem®. The successful radiolabeling of FeHA allowed for scintigraphy/X-ray and ex vivo biodistribution studies, confirming MR results and envisioning FeHA application for dual-imaging.

Dextran-coated superparamagnetic iron oxide nanoparticles for magnetic resonance imaging: evaluation of size-dependent imaging properties, storage stability and safety.

BackgroundRising criticism of currently available contrast agents for magnetic resonance imaging, either due to their side effects or limited possibilities in terms of functional imaging, evoked the need for safer and more versatile agents. We previously demonstrated the suitability of novel dextran-coated superparamagnetic iron oxide nanoparticles (SPIONDex) for biomedical applications in terms of safety and biocompatibility.MethodsIn the present study, we investigated the size-dependent cross-linking process of these particles as well as the size dependency of their imaging properties. For the latter purpose, we adopted a simple and easy-to-perform experiment to estimate the relaxivity of the particles. Furthermore, we performed an extensive analysis of the particles’ storage stability under different temperature conditions, showing their superb stability and the lack of any signs of agglomeration or sedimentation during a 12 week period.ResultsIndependent of their size, SPIONDex displayed no irritation potential in a chick chorioallantoic membrane assay. Cell uptake studies of ultra-small (30 nm) SPIONDex confirmed their internalization by macrophages, but not by non-phagocytic cells. Additionally, complement activation-related pseudoallergy (CARPA) experiments in pigs treated with ultra-small SPIONDex indicated the absence of hypersensitivity reactions.ConclusionThese results emphasize the exceptional safety of SPIONDex, setting them apart from the existing SPION-based contrast agents and making them a very promising candidate for further clinical development.

Synthesis and characterization of dextran-coated iron oxide nanoparticles.

Synthesis and characterization of iron oxide nanoparticles coated with a large molar weight dextran for environmental applications are reported. The first experiments involved the synthesis of iron oxide nanoparticles which were coated with dextran at different concentrations. The synthesis was performed by a co-precipitation technique, while the coating of iron oxide nanoparticles was carried out in solution. The obtained nanoparticles were characterized by using scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction spectrometry, Fourier transform infrared spectroscopy and superconducting quantum interference device magnetometry. The results demonstrated a successful coating of iron oxide nanoparticles with large molar weight dextran, of which agglomeration tendency depended on the amount of dextran in the coating solution. SEM and TEM observations have shown that the iron oxide nanoparticles are of about 7 nm in size.

Fucoidan Prolongs the Circulation Time of Dextran-Coated Iron Oxide Nanoparticles.

The magnetic properties and safety of dextran-coated superparamagnetic iron oxide nanoparticles (SPIONs) have facilitated their clinical use as MRI contrast agents and stimulated research on applications for SPIONs in particle imaging and magnetic hyperthermia. The wider clinical potential of SPIONs, however, has been limited by their rapid removal from circulation via the reticuloendothelial system (RES). We explored the possibility of extending SPION circulatory time using fucoidan, a seaweed-derived food supplement, to inhibit RES uptake. The effects of fucoidan on SPION biodistribution were evaluated using ferucarbotran, which in its pharmaceutical formulation (Resovist) targets the RES. Ferucarbotran was radiolabeled at the iron oxide core with technetium-99m (99mTc; t1/2 = 6 h) or zirconium-89 (89Zr; t1/2 = 3.3 days). Results obtained with 99mTc-ferucarbotran demonstrated that administration of fucoidan led to a 4-fold increase in the circulatory half-life (t1/2 slow) from 37.4 to 150 min (n = 4; P < 0.0001). To investigate whether a longer circulatory half-life could lead to concomitant increased tumor uptake, the effects of fucoidan were tested with 89Zr-ferucarbotran in mice bearing syngeneic subcutaneous (GL261) tumors. In this model, the longer circulatory half-life achieved with fucoidan was associated with a doubling in tumor SPION uptake (n = 5; P < 0.001). Fucoidan was also effective in significantly increasing the circulatory half-life of perimag-COOH, a commercially available SPION with a larger hydrodynamic size (130 nm) than ferucarbotran (65 nm). These findings indicate successful diversion of SPIONs away from the hepatic RES and show realistic potential for future clinical applications.

SYNTHESIS AND NUCLEAR MAGNETIC RELAXATION PROPERTIES OF COMPOSITE IRON OXIDE NANOPARTICLES

Superparamagnetic iron oxide nanoparticles are suitable contrast agents for magnetic resonance imaging due to their effect on proton relaxation times, and excellent biocompatibility and biodistribution in tissue. In the present study, a ferrofluid formed by dextran-coated iron oxide nanoparticles was prepared by the coprecipitation method and with subsequent steps of crosslinking and addition of functionalizations on the nanoparticle's surface (amino groups and a fluorophore). The effect of differences in the synthesis route (ratio of dextran to iron salts and temperature of the reaction) on the physico-chemical characteristics of the nanoparticles and their performance as contrast agents for magnetic resonance imaging was investigated. Overall, the nuclear magnetic relaxation times of water protons in aqueous suspensions of the nanoparticles did not show major differences among different batches, with no significant effect due to the addition of the fluorophore or changes in the dextran fraction of up to 50%. Larger reductions in the ratio of dextran to iron salts resulted in particles with slightly larger sizes, higher saturation magnetization and distinct nuclear magnetic relaxation times.

Implications of exposure to dextran-coated and uncoated iron oxide nanoparticles to developmental toxicity in zebrafish

Iron oxide nanoparticles (IONPS) have been widely investigated as a platform for a new class of multifunctional theranostic agents. They are considered biocompatible, and some formulations are already available in the market for clinical use. However, contradictory results regarding toxicity of IONPs raise a concern about the potential harm of these nanoparticles. Changes in the nanoparticle (NP) physicochemical properties or exposure media can significantly alter their behavior and, as a consequence, their toxic effects. Here, behavior and two-step RT-qPCR were employed to access the potential toxicological effects of dextran-coated IONPs (CLIO-NH2) and uncoated IONPs (UCIO) in zebrafish larvae. Animals were exposed for 7 days to NP solutions ranging from 0.1–100 μg/mL directly mixed to the system water. UCIO showed high decantation and instability in solution, altering zebrafish mortality but showing no alterations in behavior and molecular expression analysis. CLIO-NH2 exposure did not cause significant mortality or changes in hatching rate of zebrafish larvae; however, behavior and expression profiles of the group exposed to lower concentration (1 μg/mL) presented a tendency to decrease the locomotor activity and apoptotic pathway activation.

Biosynthesis of superparamagnetic polymer microbeads via simple precipitation of enzymatically synthesized short-chain amylose

Here, we report a simple and non-emulsion based approach to prepare starch-based magnetic polymer beads with well-defined size, shape and dispersibility in aqueous environment through co-precipitation of enzymatically synthesized short chain amylose (SCA) and dextran-coated iron oxide nanoparticles (Dex@IONPs). The size and morphology of magnetic polymer beads (MPBs) were controlled by employing Dex@IONPs as a seeding agent. The resulting superparamagnetic amylose microbeads (SAMBs) were readily functionalized with antibody through one step reaction using a linker protein, which showed great capture efficiency (>90%) and specificity for target bacteria present in complicated food matrix. The excellent magnetic sensitivity also enabled the SAMBs readily assembled into ordered 1D arrays by external magnetic field whose structure could permanently be fixed by SCA-mediated precipitation process.

The Cytotoxicity of Dextran-coated Iron Oxide Nanoparticles on Hela and MCF-7 Cancerous Cell Lines

Background: Recently, iron oxide nanoparticles have attracted attention in various diagnosis and treatment fields. The aim of the present study was to investigate the cytotoxicity of various concentrations and incubation times of dextran-coated iron oxide nanoparticles (DIONPs) on HeLa and MCF-7 cancerous cell lines. Methods: This in-vitro study was conducted at Pharmaceutical Sciences Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran in 2016. The dextran-coated iron oxide nanoparticles (DIONPs) uptake and cytotoxicity at different concentrations (10, 40 and 80 µg/ml) and different incubation times (6, 12 and 24 h) were assessed on HeLa and MCF-7 cell lines. The viability of the cells was measured by MTT assay. Results: DIONPs entered into the HeLa and MCF-7 cells. After 6, 12 and 24 h incubation times and in all concentrations, the viability of HeLa cells was more than 94. For MCF-7 cell line, increasing incubation time from 6 to 24 h at a concentration of 10 μg/ml decreased the cells viability from 98 to 95. When the cells were exposed to concentrations of 40 and 80 μg/ml of the nanoparticles, significant reductions in the cells viability was observed from 98 to 91.6 and from 95 to 88, respectively. Conclusion: DIONPs cytotoxicity increased by increasing the incubation time from 6 to 24 h and also increased with increasing the nanoparticles concentration from 0 to 80 μg/ml. In general, DIONPs did not cause considerable toxicity in both cell lines especially at lower concentrations. Therefore, these nanoparticles are good candidates for use in biomedical and cancer research studies.

Exogenous iron redistribution between brain and liver after administering 57Fe3O4 ferrofluid to a rat brain ventricle

The natural excretion of 57Fe enriched magnetic nanoparticles from a rat’s brain through its blood–brain barrier is studied. Dextran-coated iron oxide nanoparticles are transcranially injected into the rat’s brain ventricle. The injected nanoparticles undergo biotransformation into iron-containing proteins distributed over the brain tissues, while the exogenous iron transported from the brain to other organs is eliminated from the body over time.