Recent Progress in Superparamagnetic Iron Oxide Nanoparticles

Superparamagnetic iron oxide nanoparticles(SPIONs)have immeasurable potentials in many fields such as nanobiotechnology and biomedical engineering because of their superparamagnetic properties and small particle size.This review introduces the methods for SPIONs synthesis,including co-precipitation,thermal decomposition,microemulsion and hydrothermal reaction,and surface modification of SPIONs with organometallic and inorganic metals,surface modification for targeted drug delivery,and the use of SPIONs as a contrast agent.In addition,this article also provides an overview of recent progress in SPIONs for the treatment of glioma,lung cancer and breast cancer.

Magnetic labeling of primary murine monocytes using very small superparamagnetic iron oxide nanoparticles

Due to their very small size,nanoparticles can interact with all cells in the central nervous system.One of the most promising nanoparticle subgroups are very small superparamagnetic iron oxide nanoparticles(VSOP)that are citrate coated for electrostatic stabilization.To determine their influence on murine blood-derived monocytes,which easily enter the injured central nervous system,we applied VSOP and carboxydextran-coated superparamagnetic iron oxide nanoparticles(Resovist).We assessed their impact on the viability,cytokine,and chemokine secretion,as well as iron uptake of murine blood-derived monocytes.We found that(1)the monocytes accumulated VSOP and Resovist,(2)this uptake seemed to be nanoparticle-and time-dependent,(3)the decrease of monocytes viability was treatment-related,(4)VSOP and Resovist incubation did not alter cytokine homeostasis,and(5)overall a 6-hour treatment with 0.75 mM VSOP-R1 was probably sufficient to effectively label monocytes for future experiments.Since homeostasis is not altered,it is safe to label blood-derived monocles with VSOP.VSOP labeled monocytes can be used to study injured central nervous system sites further,for example with drug-carrying VSOP.

Current status of superparamagnetic iron oxide contrast agents for liver magnetic resonance imaging

Five types of superparamagnetic iron oxide （SPIO）,i.e. Ferumoxides （Feridex？ Ⅳ, Berlex Laboratories）,Fe r u c a r b o t ra n （ Re s ov i s t？, B aye r H e a l t h c a re ） ,Ferumoxtran-10 （AMI-227 or Code-7227, Combidex？, AMAG Pharma; Sinerem？, Guerbet）, NC100150（Clariscan？, Nycomed,） and （VSOP C184, Ferropharm）have been designed and clinically tested as magneticresonance contrast agents. However, until nowResovist？ is current available in only a few countries.The other four agents have been stopped for furtherdevelopment or withdrawn from the market. AnotherSPIO agent Ferumoxytol （Feraheme） is approved forthe treatment of iron deficiency in adult chronic kidneydisease patients. Ferumoxytol is comprised of ironoxide particles surrounded by a carbohydrate coat, andit is being explored as a potential imaging approach forevaluating lymph nodes and certain liver tumors.

Biodistribution and Toxicity Assessment of Superparamagnetic Iron Oxide Nanoparticles In Vitro and In Vivo

Biodistribution and toxicity assessment are critical for safe clinical use of newly developed medicines.Superparamagnetic iron oxide nanoparticles (SPION)are effective carriers for targeted drug delivery.This study aimed to examine the toxicity and biodistribution of SPION coated with polyethylenimine (PEI)(SPION-PEI)designed for small interfering RNA (siRNA) delivery both in vitro and in vivo.SPION-PEI/siRNA complexes were prepared at different weight ratios.Cytotoxic effects of SPION-PEI/siRNA on HSC-T6 cell viability were determined by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT).Rats were divided into three groups:a control group,a normal-saline group and a SPION-PEI/siRNA group.After a single intravenous injection,in vivo nanoparticle biodistribution and accumulation were evaluated by Prussian blue staining in the heart,liver,spleen,lung and kidney 8 h,24 h,and 7 days after the injection.Their distribution was histologically studied at the three time points by measuring ironpositive areas (μm2)in organ sections stained with Prussian blue.The same organs were analyzed by H&E staining for any possible histopathological changes.Furthermore,biochemical indexes such as alanine amino transaminase (ALT),aspartate transaminase (AST),blood urea nitrogen (BUN)and creatinine (CREA)were also assessed at all experimental time points.Electrophoresis exhibited that the SPION-PEI could retard siRNA altogether at weight ratios above 4.MTT assay showed that SPION-PEI loaded with siRNA had low cytotoxicity.In vivo study revealed that the liver and spleen were the major sites of SPION-PEI/siRNA deposition.The iron content was significantly increased in the liver and spleen,peaking 24 h after intravenous injection and then declining gradually.No evidence was found of irreversible histopathological damage to any of the organs tested.These results suggested that most SPION-PEI/siRNA complexes were distributed in the liver and spleen,which might be the target organs of SPION-PEI/siRNA complexes.SPION- PEI/siRNA may serve as in vivo carrier for biomedical medicines.

Distribution of c-erbB2 Antisense Probe Labeled with Superparamagnetic Iron Oxide Nanoparticles in the Major Organs of Mice on MR Imaging

Background: The aim of this study was to investigate the distribution of the c-erbB2 antisense probe labeled with superparamagnetic iron oxide nanoparticles in the major organs of mice by MR imaging. Methods: Sixty BALB/c mice were randomly divided into experimental and control groups. MR scans were performed in each mouse of the experimental group at five different time points (10, 30, 60, 180 and 360 min) after injection of the antisense probe. The signal from each major organ (liver, spleen, heart, kidney and muscle tissue) in comparison with the background signal (signal to noise ratio) was determined at each time point as a measure of the distribution of the antisense probe. Six control mice were killed at each of the same time points and the organs immediately removed for determination of their iron content. Results: After injection of the antisense probe, the highest enrichment of the probe was seen in the spleen, reaching a peak at 180 min, followed by the liver, muscle, heart and kidney. Conclusions: MR imaging can visualize the distribution of c-erbB2 antisense probe labeled with superparamagnetic iron oxide nanoparticles in the major organs of mice, and this may provide the basis for further in vivo studies of MR imaging time and dose selection.

Remote induction of in situ hydrogelation in a deep tissue,using an alternating magnetic field and superparamagnetic nanoparticles

In situ hydrogelation systems, such as transdermal polymerization, allow forexternal control over the gelation processes in a minimally invasive way. Recently,a novel system consisting of near-infrared （NIR） light and plasmonic nano-materials was demonstrated to cause in vivo transdermal gelation. However,NIR light is not sufficient for gelation induction in deep tissues owing to itslimited penetration into tissues. To overcome this problem, here we developedan alternating magnetic field （AMF）-inducible hydrogelation system withsuperparamagnetic iron oxide nanoparticles （SPIONs）, by which a deep-tissue-penetrating AMF can induce heat generation in the SPIONs and temperatureelevation （≥ 43℃）, leading to initiation of thermal polymerization of poly（ethyleneglycol） diacrylate. The feasibility of our AMF-inducible hydrogelation wassuccessfully demonstrated using thick porcine muscle tissues （〉 2 cm）, whereasthe NIR light-based hydrogelation system could induce gelation only in tissuesthinner than several millimeters. Cell viability assays indicated cytocompatibilityof the AMF-inducible hydrogelation for cell encapsulation and delivery. In vivohydrogelation in rat muscle tissues further validated in situ hydrogelation indeep muscle tissues of a living animal. This AMF-inducible hydrogelationsystem may overcome the conventional problems of depth limitation and shouldextend the applicable area of on-demand injectable hydrogel systems for tissueengineering and drug delivery applications.

Superparamagnetic CoFe2O4@Au with High Specific Absorption Rate and Intrinsic Loss Power for Magnetic Fluid Hyperthermia Applications

CoFe2O4 nanoparticles(NPs)and surface modified with gold(Au)have been synthesized by a thermal decomposition method.The obtained NPs and formation of CoFe2O4@Au core–shell(CS)were confirmed by characterizing their structural and optical properties using X-ray powder diffraction(XRD)patterns,Fourier transform infrared spectroscopy,Raman spectroscopy,UV–Visible and photoluminescence studies.Morphological and compositional studies were carried out using high-resolution transmission electron microscopy and energy-dispersive X-ray spectroscopy,while the magnetic properties were determined using alternating gradient magnetometer and Mossbauer to define the magneto-structural effects of shell formation on the core NPs.Induction heating properties of CoFe2O4 and CoFe2O4@Au CS magnetic nanoparticles(MNPs)have been investigated and correlated with magneto-structural properties.Specific absorption rate and intrinsic loss power were calculated for these MNPs within the human tolerable range of frequency and amplitude,suggesting their potential in magnetic fluid hyperthermia therapy for possible cancer treatment.

Synthesis and application of superparamagnetic iron oxide nanoparticles in targeted therapy and imaging of cancer

Superparamagnetic iron oxide(SPIO)nanoparticles have become a popular strategy of cancer treatment and molecular imaging because of their versatile properties and biocompatibility.A variety of studies have shown the exciting potential of functionalized SPIO nanoparticles,such as surface-coated,targeted ligandconjugated,and/or drug-loaded SPIO nanoparticles,as powerful tools for targeted imaging and therapy.Moreover,the applications of SPIO nanoparticles that integrate diagnosis and therapy in SPIO nanoparticles facilitate the monitoring of therapeutic efficacy during treatment.In the present review,we primarily concentrate on the recent advancements in the field of SPIO nanoparticles in terms of synthesis,targeted therapy,and cancer imaging.

MRI tracking of human Wharton’s jelly stem cells seeded onto acellular dermal matrix labeled with superparamagnetic iron oxide nanoparticles in burn wounds

Background:In vivo cell tracking after transplantation in regenerative medicine remains an unmet challenge and limits current understanding of the wound healing mechanism through cell-based therapies.This study investigated tracking of human Wharton’s jelly stem cells(hWJSCs)seeded onto an acellular dermal matrix(ADM)and labeled with superparamagnetic iron oxide nanoparti-cles(SPIONs)by magnetic resonance imaging(MRI)in burn injury.Method:The hWJSCs were characterized and assessed for growth kinetics.A total of 30 rats were enrolled in three equal groups.Group 1 underwent scald burn injury left without treatment,the group 2 was treated by an ADM that was prepared from cosmetic surgery skin samples and the group 3 received hWJSCs labeled with SPIONs seeded onto an ADM.Tensile strength was evaluated before and after interventions,real time PCR assessed apoptosis,and Prussian blue staining,scanning electron microscopy(SEM)and MRI were used for the tracking of labeled cells.Results:The hWJSCs exhibited mesenchymal stem cell properties.Population doubling time was 40.1 hours.SPIONs did not show any toxic effect.The hWJSCs seeded onto an ADM decreased Bax and increased Bcl-2 gene expression.Internalization of SPIONs within hWJSCs was confirmed by Prussian blue staining,SEM and MRI until day 21.There was a significant difference between the Young’s moduli of normal skin and the group receiving hWJSCs seeded onto an ADM.Histological observations and SEM imaging confirmed that MRI is an accurate method to track SPION-labeled hWJSCs in vivo.Conclusions:This study showed that SPION labeling coupled with MRI can be used to further understand the fate of stem cells after transplantation in a burn model.

Integration of PEG-conjugated gadolinium complex and superparamagnetic iron oxide nanoparticles as T_(1)-T_(2) dual-mode magnetic resonance imaging probes

The T_(1)-T_(2) dual-mode probes for magnetic resonance imaging(MRI)can non-invasively acquire comprehensive information of different tissues or generate self-complementary information of the same tissue at the same time,making MRI a more flexible imaging modality for complicated applications.In this work,three Gadolinium-diethylene-triaminepentaaceticacid(Gd-DTPA)complex conjugated superparamagnetic iron oxide(SPIO)nanoparticles with different Gd/Fe molar ratio(0.94,1.28 and 1.67)were prepared as T_(1)-T_(2) dual-mode MRI probes,named as SPIO@PEG-GdDTPA0.94,SPIO@PEGGdDTPA1.28 and SPIO@PEG-GdDTPA1.67,respectively.All SPIO@PEG-GdDTPA nanocomposites with 8 nm spherical SPIO nanocrystals showed good Gd3þchelate stability.SPIO@PEG-GdDTPA0.94 nanocomposites with lowest Gd/Fe molar ratio show no cytotoxicity to Raw 264.7 cells as compared to SPIO@PEG-GdDTPA1.28 and SPIO@PEG-GdDTPA1.67.SPIO@PEG-GdDTPA0.94 nanocomposites with r1(8.4mM^(-1)s^(-1)),r2(83.2mM^(-1)s^(-1))and relatively ideal r2/r1 ratio(9.9)were selected for T_(1)-T_(2) dual-mode MRI of blood vessels and liver tissue in vivo.Good contrast images were obtained for both cardiovascular system and liver in animal studies under a clinical 3 T scanner.Importantly,one can get high-quality contrast-enhanced blood vessel images within the first 2 h after contrast agent administration and acquire liver tissue anatomy information up to 24 h.Overall,the strategy of one shot of the dual mode MRI agent could bring numerous benefits not only for patients but also to the radiologists and clinicians,e.g.saving time,lowering side effects and collecting data of different organs sequentially.

Magnetic entropy and magnetocalonc effects in nanometer superparamagnetic system

Calculation on magnetic entropy in a nanostructured superparamagnetic system has been carried out by means of both classical statistical thermodynamics and quantum theory. It turns out that there exists an optimal particle size for nanometer superparamagnets at which a maximum change of magnetic entropy is achieved, and that nanometer superparamagnets have an advantage of enhanced magnetocaloric effects over the conventional paramagnets within the wide distribution of particle size of nanometer materials. The enhanced magnetocaloric effects of nanometer superparamagnets revealed by the theoretical calculation mentioned above have been proved experimentally in the investigation of nanocomposite solid of Gd-Y alloy.

Development and in vitro study of a bi-specific magnetic resonance imaging molecular probe for hepatocellular carcinoma

BACKGROUND Hepatocellular carcinoma(HCC)ranks second in terms of cancer mortality worldwide.Molecular magnetic resonance imaging(MRI)targeting HCC biomarkers such as alpha-fetoprotein(AFP)or glypican-3(GPC3)offers new strategies to enhance specificity and help early diagnosis of HCC.However,the existing iron oxide nanoparticle-based MR molecular probes singly target AFP or GPC3,which may hinder their efficiency to detect heterogeneous micro malignant HCC tumors<1 cm(MHCC).We hypothesized that the strategy of double antibody-conjugated iron oxide nanoparticles which simultaneously target AFP and GPC3 antigens may potentially be used to overcome the tumor heterogeneity and enhance the detection rate for MRI-based MHCC diagnosis.AIM To synthesize an AFP/GPC3 double antibody-labeled iron oxide MRI molecular probe and to assess its impact on MRI specificity and sensitivity at the cellular level.METHODS A double antigen-targeted MRI probe for MHCC anti-AFP-USPIO-anti-GPC3(UAG)was developed by simultaneously conjugating AFP andGPC3 antibodies to a 5 nm ultra-small superparamagnetic iron oxide nanoparticle(USPIO).At the same time,the singly labeled probes of anti-AFP-USPIO(UA)and anti-GPC3-USPIO(UG)and non-targeted USPIO(U)were also prepared for comparison.The physical characterization including morphology(transmission electron microscopy),hydrodynamic size,and zeta potential(dynamic light scattering)was conducted for each of the probes.The antigen targeting and MRI ability for these four kinds of USPIO probes were studied in the GPC3-expressing murine hepatoma cell line Hepa1-6/GPC3.First,AFP and GPC3 antigen expression in Hepa1-6/GPC3 cells was confirmed by flow cytometry and immunocytochemistry.Then,the cellular uptake of USPIO probes was investigated by Prussian blue staining assay and in vitro MRI(T2-weighted and T2-map)with a 3.0 Tesla clinical MR scanner.RESULTS Our data showed that the double antibody-conjugated probe UAG had the best specificity in targeting Hepa1-6/GPC3 cells expressing AFP and GPC3 antigens compared with single antibody-conjugated and unconjugated USPIO probes.The iron Prussian blue staining and quantitative T2-map MRI analysis showed that,compared with UA,UG,and U,the uptake of double antigen-targeted UAG probe demonstrated a 23.3%(vs UA),15.4%(vs UG),and 57.3%(vs U)increased Prussian stained cell percentage and a 14.93%(vs UA),9.38%(vs UG),and 15.3%(vs U)reduction of T2 relaxation time,respectively.Such bi-specific probe might have the potential to overcome tumor heterogeneity.Meanwhile,the coupling of two antibodies did not influence the magnetic performance of USPIO,and the relatively small hydrodynamic size(59.60±1.87 nm)of double antibodyconjugated USPIO probe makes it a viable candidate for use in MHCC MRI in vivo,as they are slowly phagocytosed by macrophages.CONCLUSION The bi-specific probe presents enhanced targeting efficiency and MRI sensitivity to HCC cells than singly-or non-targeted USPIO,paving the way for in vivo translation to further evaluate its clinical potential.

Magnet-targeted delivery of bone marrow-derived mesenchymal stem cells improves therapeutic efficacy following hypoxic-ischemic brain injury

hypoxicischemic brain injury;however,the therapeutic efficacy of bone marrow-derived mesenchymal stem cells largely depends on the number of cells that are successfully transferred to the target.Magnet-targeted drug delivery systems can use a specific magnetic field to attract the drug to the target site,increasing the drug concentration.In this study,we found that the double-labeling using superparamagnetic iron oxide nanoparticle and poly-L-lysine(SPIO-PLL)of bone marrow-derived mesenchymal stem cells had no effect on cell survival but decreased cell proliferation 48 hours after labeling.Rat models of hypoxic-ischemic brain injury were established by ligating the left common carotid artery.One day after modeling,intraventricular and caudal vein injections of 1×105 SPIO-PLL-labeled bone marrow-derived mesenchymal stem cells were performed.Twenty-four hours after the intraventricular injection,magnets were fixed to the left side of the rats’heads for 2 hours.Intravoxel incoherent motion magnetic resonance imaging revealed that the perfusion fraction and the diffusion coefficient of rat brain tissue were significantly increased in rats treated with SPIO-PLL-labeled cells through intraventricular injection combined with magnetic guidance,compared with those treated with SPIO-PLL-labeled cells through intraventricular or tail vein injections without magnetic guidance.Hematoxylin-eosin and terminal deoxynucleotidyl transferase dUTP nick-end labeling(TUNEL)staining revealed that in rats treated with SPIO-PLL-labeled cells through intraventricular injection under magnetic guidance,cerebral edema was alleviated,and apoptosis was decreased.These findings suggest that targeted magnetic guidance can be used to improve the therapeutic efficacy of bone marrow-derived mesenchymal stem cell transplantation for hypoxic-ischemic brain injury.This study was approved by the Animal Care and Use Committee of The Second Hospital of Dalian Medical University,China(approval No.2016-060)on March 2,2016.

Noninvasive in vivo cell tracking using molecular imaging:A useful tool for developing mesenchymal stem cell-based cancer treatment

Mounting evidence has emphasized the potential of cell therapies in treating various diseases by restoring damaged tissues or replacing defective cells in the body.Cell therapies have become a strong therapeutic modality by applying noninvasive in vivo molecular imaging for examining complex cellular processes,understanding pathophysiological mechanisms of diseases,and evaluating the kinetics/dynamics of cell therapies.In particular,mesenchymal stem cells(MSCs)have shown promise in recent years as drug carriers for cancer treatment.They can also be labeled with different probes and tracked in vivo to assess the in vivo effect of administered cells,and to optimize therapy.The exact role of MSCs in oncologic diseases is not clear as MSCs have been shown to be involved in tumor progression and inhibition,and the exact interactions between MSCs and specific cancer microenvironments are not clear.In this review,a multitude of labeling approaches,imaging modalities,and the merits/demerits of each strategy are outlined.In addition,specific examples of the use of MSCs and in vivo imaging in cancer therapy are provided.Finally,present limitations and future outlooks in terms of the translation of different imaging approaches in clinics are discussed.

铁酸钴纳米粒子:室温下点击合成亚芳基巴比妥酸衍生物的高效可磁性分离多相催化剂(英文)

A coprecipitation method was used to synthesize superparamagnetic CoFe2O4 nanoparticles without using any capping agents/surfactants. The prepared nanoparticles were characterized using Fourier transform infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, X-ray diffraction, a vibrating sample magnetometer (VSM), N2 adsorption and thermogravimetric/differential thermal analysis/differential thermal gravimetry techniques. The synthesized spinel CoFe2O4 nanoparticles had an average size of 2-8 nm with a high surface area (140.9 m2/g). The field-dependent magnetization, demonstrated by VSM and saturation magnetization, was found to be 1.77 emu/g. An efficient method was used for the synthesis of arylidene barbituric acid derivatives using CoFe2O4 magnetic nanoparticles as a magnetically separable and reusable catalyst in aqueous ethanol. The attractive features of this synthetic protocol were very short reaction time, high yields, high turnover frequency, simple work-up procedure, economy, a clean reaction methodology, and chemoselectivity, as well as provision of an ecofriendly and green synthesis.

Fabrication of magnetically responsive anti-fouling and easy-cleaning nanofiber membrane and its application for efficient oil-water emulsion separation

The magnetically responsive anti-fouling nanofiber membrane(MRANM)was fabricated for efficient oilwater emulsion separation,which could be cleaned using oscillating magnetic field.MRANM was prepared by grafting superparamagnetic Fe_(3)O_(4) nanoparticles onto the surface of electrospun polyacrylonitrile nanofiber membrane(PANM).Compared with PANM,the water contact angle of MRANM decreased from 104°to 0°,indicating that the hydrophilicity of the membrane was significantly improved.For the emulsions of hexadecane,octane and rapeseed oil,the separation efficiency was 98.04%,96.59%and 92.67%,respectively.After the treatments in oscillating magnetic field,the separation efficiency kept above 95%after 8 times recycling,which indicated that the MRANM had good regenerability and reusability.The as-fabricated membrane with magnetic responsiveness facilitated an effective method for solving the membrane fouling problem during practical applications of separation high viscosity oil-water emulsion.

Suzuki Reaction of Aryl Bromides Using a Phosphine-Free Magnetic Nanoparticle-Supported Palladium Catalyst

A palladium catalyst immobilized on superparaganetic nanoparticles was prepared with a palladium loading of 0.30 mmol/g. The catalyst was characterized using X-ray diffraction, scanning electron microscopy, transmission electron microscopy, vibrating sample magnetometry, thermogravimetric analysis, Fourier transform infrared, atomic absorption spectrophotometry, and nitrogen adsorption. The immobilized palladium catalyst was an efficient catalyst without added phosphine ligands for the Suzuki cross-coupling reaction of several aryl bromides with phenylboronic acid. The recovery of catalyst was simply by magnetic decantation in the presence of a magnet. The immobilized palladium catalyst can be reused many times without significant degradation in catalytic activity. No leaching of active palladium species into the reaction solution was detected.

Magnetic nanoparticles conjugated with “RPE cell-MCP-1 antibody-VEGF antibody” compounds for the targeted therapy of age-related macular degeneration: a hypothesis

Age-related macular degeneration(AMD) is the leading cause of vision loss in the elderly throughout the world. Treatment of AMD utilizing retinal pigment epithelium(RPE) transplantation represents a promising therapy. However, simplex RPE transplantation can only replace the diseased RPE cells, but has no abilities to stop the development of AMD. It has been indicated that oxidization triggers the development of AMD by inducing the dysfunction and degeneration of RPE cells, which results in the upregulation of local monocyte chemotactic protein-1(MCP-1) expression. MCP-1 induces macrophage recruiment which triggers local inflammation. As a result, the expression of vascular endothelial growth factor(VEGF) is upregulated by MCP-1mediated inflammation and results in the formation of choroidal neovascularization(CNV). We accordingly propose a targeted therapy of AMD by subretinal transplanting the compound of RPE cell, MCP-1 antibody, and VEGF antibody and using a magnetic system to guide RPE cell compounds conjugated with superparamagnetic iron oxide nanoparticles(SPIONs). Furthermore, SPION-labelled RPE cells can be tracked and detected in vivo by non-invasive magnetic resonance imaging(MRI). This novel RPE cell transplantation methodology seems very promising to provide a new therapeutic approach for the treatment of AMD.

Effect of Nd Doping on Nanosized Mn-Zn Ferrite

Nanosized Mn-Zn ferrite doped with Nd （Mn 0.6Zn 0.4NdxFe 2-xO4） were fabricated by hydrothermal precipitation route and studied by XRD, TEM, DSC and VSM. The effects of Nd doping on manganese zinc ferrites were discussed. The results show that the samples with a small amount of Nd doping are spinel crystal structure and uniformly nanosized particles with little aggregation. DSC analysis of Mn 0.6Zn 0.4Fe2O4 and Mn 0.6Zn 0.4Nd 0.06Fe 1.94O4 samples both present two exothermic peaks ascribed to the redistribution of Mn 2+, Zn 2+ and Fe 3+ ions in the two sub-lattices （tetrahedral （A） and octahedral （B） sites）, and the oxidation of Mn 2+-ions at higher temperatures respectively. The saturation magnetization （Ms） for Mn 0.6Zn 0.4NdxFe 2-xO4 ferrites increase with （x） up to 0.06 and decrease for higher concentrations. And supermagnetic behavior was observed at 25 ℃ in the M-H loops of Mn 0.6Zn 0.4Fe2O4 and Mn 0.6Zn 0.4Nd 0.06Fe 1.94O4 samples for their extremely small sizes.

Imaging C-Fos Gene Expression in Burns Using Lipid Coated Spion Nanoparticles

MR imaging of gene transcription is important as it should enable the non-invasive detection of mRNA alterations in disease. A range of MRI methods have been proposed for in vivo molecular imaging of cells based on the use of ultra- small super-paramagnetic iron oxide (USPIO) nanoparticles and related susceptibility weighted imaging methods. Al-though immunohistochemistry can robustly differentiate the expression of protein variants, there is currently no direct gene assay technique that is capable of differentiating established to differentiate the induction profiles of c-Fos mRNA in vivo. To visualize the differential FosB gene expression profile in vivo after burn trauma, we developed MR probes that link the T2* contrast agent [superparamagnetic iron oxide nanoparticles (SPION)] with an oligodeoxynucleotide (ODN) sequence complementary to FosB mRNA to visualize endogenous mRNA targets via in vivo hybridization. The presence of this SPION-ODN probe in cells results in localized signal reduction in T2*-weighted MR images, in which the rate of signal reduction (R2*) reflects the regional iron concentration at different stages of amphetamine (AMPH) exposure in living mouse tissue. Our aim was to produce a superior contrast agent that can be administered using sys- temic as opposed to local administration and which will target and accumulate at sites of burn injury. Specifically, we developed and evaluated a PEGylated lipid coated MR probe with ultra-small super-paramagnetic iron oxide nanoparti- cles (USPION, a T2 susceptibility agent) coated with cationic fusogenic lipids, used for cell transfection and gene de- livery and covalently linked to a phosphorothioate modified oligodeoxynucleotide (sODN) complementary to c-Fos mRNA (SPION-cFos) and used the agent to image mice with leg burns. Our study demonstrated the feasibility of monitoring burn injury using MR imaging of c-Fos transcription in vivo, in a clinically relevant mouse model of burn injury for the first time.