Usefulness of Magnetic Particle Imaging for Monitoring the Effect of Magnetic Targeting

Purpose: Magnetic targeting refers to the attachment of therapeutic agents to magnetizable particles such as magnetic nanoparticles (MNPs) and then applying magnetic fields to concentrate them to the targeted region such as solid tumors. The purpose of this study was to investigate the usefulness of magnetic particle imaging (MPI) for monitoring the effect of magnetic targeting using tumor-bearing mice. Materials and Methods: Colon-26 cells (1 × 106 cells) were implanted into the backs of eight-week-old male BALB/c mice. When the tumor volume reached approximately 100 mm3, the mice were divided into treated (n = 8) and untreated groups (n = 8). The tumors in the treated group were directly injected with MNPs (Resovist?, 250 mM) and a neodymium magnet was attached to the tumor surface, whereas the magnet was not attached to the tumor in the untreated group. The mice were imaged using our MPI scanner and the average and maximum MPI values were obtained by drawing a region of interest (ROI) on the tumor, with the threshold value for extracting the contour of the tumor being taken as 40% of the maximum MPI value in the ROI. The relative tumor volume growth (RTVG) was calculated from (V ? V0)/V0, where V0 and V represented the tumor volume immediately before and after the injection of MNPs, respectively. Results: The average and maximum MPI values in the treated group were significantly higher than those in the untreated group 3 days after the injection of MNPs, suggesting the effectiveness of magnetic targeting. There were no significant differences in RTVG between the two groups. Conclusion: Our preliminary results suggest that MPI is useful for monitoring the effect of magnetic targeting.

Process Modeling of Ferrofluids Flow for Magnetic Targeting Drug Delivery

Among the proposed techniques for delivering drugs to specific sites within the human body, magnetic targeting drug delivery surpasses due to its non-invasive character and its high targeting efficiency. Although there have been some analyses theoretically for magnetic drug targeting, very few researchers have addressed the hydrodynamic models of magnetic fluids in the blood vessel of human body. This paper presents a mathematical model to describe the hydrodynamics of ferrofluids as drug carriers flowing in a blood vessel under the applied magnetic field. A 3D flow field of magnetic particles in a blood vessel model is numerically simulated in order to further understand clinical application of magnetic targeting drug delivery. Simulation results show that magnetic nanoparticles can be enriched in a target region depending on the applied magnetic field intensity. Magnetic resonance imaging confirms the enrichment of ferrofluids in a desired body tissue of Sprague-Dawley rats. The simulation results coincide with those animal experiments. Results of the analysis provide the important information and can suggest strategies for improving delivery in favor of the clinical application.

Hydrodynamic modeling of ferrofluid flow in magnetic targeting drug delivery

Among the proposed techniques for delivering drugs to specific locations within human body, magnetic drug targeting prevails due to its non-invasive character and its high targeting efficiency. Magnetic targeting drug delivery is a method of carrying drug-loaded magnetic nanoparticles to a target tissue target under the applied magnetic field. This method increases the drug concentration in the target while reducing the adverse side-effects. Although there have been some theoretical analyses for magnetic drug targeting, very few researchers have addressed the hydrodynamic models of magnetic fluids in the blood vessel. A mathematical model is presented to describe the hydrodynamics of ferrofiuids as drug carriers flowing in a blood vessel under the applied magnetic field. In this model, magnetic force and asymmetrical force are added, and an angular momentum equation of magnetic nanoparticles in the applied magnetic field is modeled. Engineering approximations are achieved by retaining the physically most significant items in the model due to the mathematical complexity of the motion equations. Numerical simulations are performed to obtain better insight into the theoretical model with computational fluid dynamics. Simulation results demonstrate the important parameters leading to adequate drug delivery to the target site depending on the magnetic field intensity, which coincident with those of animal experiments. Results of the analysis provide important information and suggest strategies for improving delivery in clinical application.

Catalase-imprinted Fe3O4/Fe@fibrous SiO2/polydopamine nanoparticles： An integrated nanoplatform of magnetic targeting, magnetic resonance imaging, and dual-mode cancer therapy

Recent advances in the research on the molecular mechanism of cell death and methods for preparation of nanomaterials make the integration of various therapeutic approaches, targeting, and imaging modes into a single nanoscale complex a new trend for the development of future nanotherapeutics. Hence, a novel ellipsoidal composite nanoplatform composed of a magnetic Fe3O4/Fe nanorod core （-120 nm） enwrapped by a catalase （CAT）-imprinted fibrous SiO2/ polydopamine （F-SiO2/PDA） shell with thickness 70 nm was prepared in this work. In vitro experiments showed that the Fe3O4/Fe@F-SiO2/PDA nanoparticles can selectively inhibit the bioactivity of CAT in tumor cells by the molecular imprinting technique. As a result, the H2O2 level in tumor cells was elevated dramatically. At the same time, the Fe304FFe core released Fe ions to catalyze the conversion of H2O2 to ＊OH in tumor cells. Eventually, the concentration of ＊OH in tumor cells rapidly rose to a lethal level thus triggering apoptosis. Combined with the remarkable near-infrared light （NIR） photothermal effect of the CAT- imprinted PDA layer, the Fe3O4/Fe@F-SiO2/PDA nanoparticles can effectively kill MCF-7, HeLa, and 293T tumor cells but are not toxic to nontumor cells. Furthermore, these nanoparticles show good capacity for magnetic targeting and suitability for magnetic resonance imaging （MRI）. Therefore, the integrated multifunctional nanoplatform opens up new possibilities for high-efficiency visual targeted nonchemo therapy for cancer.

Magnetic Biliary Stent Targeting to Treat Hepatoma Combining with Magnetic Nanoparticles

To evaluate the effect of targeting to hepatoma treated by magnetic biliary stent combining with magnetic nanoparticle containing 5-fluorouracil （5-FU）, thirty-two nude mice modes with transplanted hepatoma were divided equally into four groups randomly. Experimental group received magnetic biliary stent and magnetic nanoparticles containing 5-FU. The tumor volume and pathomorphology of all groups was measured. The tumor control rate of the experimental group provided magnetic biliary stent wires and magnetic nanoparticles containing 5-FU is remarkably higher than three other control groups, showing significant curative effect. More apoptosis of tumor cells could be detected easily in experimental group. There are more apoptotic bodies and phagotrophic magnetic particle in apoptosis cells of experimental group under electron microscope. Magnetic biliary stent combining with magnetic nanoparticle containing 5-FU could inhibit the growth of hepatoma, and its curative effect is more remarkable than the traditional methods based on external magnetic fields.

In Vitro Targeted Magnetic Delivery and Tracking of Superparamagnetic Iron Oxide Particles Labeled Stem Cells for Articular Cartilage Defect Repair

To assess a novel cell manipulation technique of tissue engineering with respect to its ability to augment superparamagnetic iron oxide particles （SPIO） labeled mesenchymal stem cells （MSCs） density at a localized cartilage defect site in an in vitro phantom by applying magnetic force. Meanwhile, non-invasive imaging techniques were use to track SPIO-labeled MSCs by magnetic resonance imaging （MRI）. Human bone marrow MSCs were cultured and labeled with SPIO. Fresh degenerated human osteochondral fragments were obtained during total knee arthroplasty and a cartilage defect was created at the center. Then, the osteochondral fragments were attached to the sidewalls of culture flasks filled with phosphate-buffered saline （PBS） to mimic the human joint cavity. The SPIO-labeled MSCs were injected into the culture flasks in the presence of a 0.57 Tesla （T） magnetic force. Before and 90 min after cell targeting, the specimens underwent T2-weighted turbo spin-echo （SET2WI） sequence of 3.0 T MRI. MRI results were compared with histological findings. Macroscopic observation showed that SPIO-labeled MSCs were steered to the target region of cartilage defect. MRI revealed significant changes in signal intensity （P0.01）. HE staining exibited that a great number of MSCs formed a three-dimensional （3D） cell ＂sheet＂ structure at the chondral defect site. It was concluded that 0.57 T magnetic force permits spatial delivery of magnetically labeled MSCs to the target region in vitro. High-field MRI can serve as an very sensitive non-invasive technique for the visualization of SPIO-labeled MSCs.

A numerical survey of parameters to reach ignition condition for axial compression of a large-sized field reversed configuration

Field reversed configuration(FRC)is widely considered as an ideal target plasma for magnetoinertial fusion.However,its confinement and stability,both proportional to the radius,will deteriorate inevitably during radial compression.Hence,we propose a new fusion approach based on axial compression of a large-sized FRC.The axial compression can be made by plasma jets or plasmoids converging onto the axial ends of the FRC.The parameter space that can reach the ignition condition while preserving the FRC's overall quality is studied using a numerical model based on different FRC confinement scalings.It is found that ignition is possible for a large FRC that can be achieved with the current FRC formation techniques if compression ratio is greater than 50.A more realistic compression is to combine axial with moderate radial compression,which is also presented and calculated in this work.

Superparamagnetic iron oxide nanoparticle targeting of adipose tissue-derived stem cells in diabetes-associated erectile dysfunction

Erectile dysfunction （ED） is a major complication of diabetes, and many diabetic men with ED are refractory to common ED therapies. Adipose tissue-derived stem cells （ADSCs） have been shown to improve erectile function in diabetic animal models. However, inadequate cell homing to damaged sites has limited their efficacy. Therefore, we explored the effect of ADSCs labeled with superparamagnetic iron oxide nanoparticles （SPIONs） on improving the erectile function of streptozotocin-induced diabetic rats with an external magnetic field. We found that SPIONs effectively incorporated into ADSCs and did not exert any negative effects on stem cell properties. Magnetic targeting of ADSCs contributed to long-term cell retention in the corpus cavernosum and improved the erectile function of diabetic rats compared with ADSC injection alone. In addition, the paracrine effect of ADSCs appeared to play the major role in functional and structural recovery. Accordingly, magnetic field-guided ADSC therapy is an effective approach for diabetes-associated ED therapy.

Formation of Field Reversed Configuration (FRC) on the Yingguang-I device

As a hybrid approach to realizing fusion energy,Magnetized Target Fusion(MTF)based on the Field Reversed Configuration(FRC),which has the plasma density and confinement time in the range between magnetic and inertial confinement fusion,has been recently widely pursued around the world.To investigate the formation and confinement of the FRC plasma injector for MTF,the Yingguang-I,which is an FRC test device and contains a multi-bank program-discharged pulsed power sub-system,was constructed at the Institute of Fluid Physics(IFP),China.This paper presents the pulsed power components and their parameters of the device in detail,then gives a brief description of progress in experiments of FRC formation.Experimental results of the pulsed power sub-system show that the peak current/magnetic field of 110 kA/0.3 T,10 kA/1.2 Tand 1.7 MA/3.4 Twere achieved in the bias,mirror and q-pinch circuits with quarter cycle of 80 ms,700 ms and 3.8 ms respectively.The induced electric field in the neutral gas was greater than 0.25 kV/cm when the ionization bank was charged to 70 kV.With H_(2) gas of 8 Pa,the plasma target of density 10^(16) cm^(-3),separatrix radius 4 cm,half-length 17 cm,equilibrium temperature 200 eV and lifetime 3 ms(approximately the half pulse width of the reversed field)have been obtained through the q-pinch method when the bias,mirror,ionization and θ-pinch banks were charged to 5 kV,5 kV,55 kV and ±45 kV respectively.The images from the high-speed end-on framing camera demonstrate the formation processes of FRC and some features agree well with the results with the two-dimension magneto hydrodynamics code(2D-MHD).

Formation Process of Magnetized Fusion Target on the YingGuang 1 Device

Magnetized target fusion is an alternative method to fulfill the goal of controlled fusion, which combines advan- tages of both magnetic confinement fusion and inertial confinement fusion since its parameter space lies between the two traditional ways. Field reversed configuration （FFtC） is a good candidate of magnetized targets due to its translatable, compressible, high /3 and high energy density properties. Dynamic formation process of high density FFtC is observed on the YingGuang 1 device for the first time in China. The evolution of a magnetic field is detected with magnetic probes, and the compression process can be clearly seen from images taken with a high-speed multi-frame CCD camera. The process is also studied with two-dimensional magneto hydrodynamic code MPF-2D theoretically, and the results agree well with the experiment. Combining the experimental data and the theoretical analysis, the length of the formed FRC is about 39 cm, the diameter is about 2-2. 7cm, the average density is 1.3× 1016 cm-3, and the average temperature is 137eV.

Sorafenib delivery nanoplatform based on superpara- magnetic iron oxide nanoparticles magnetically targets hepatocellular carcinoma

Currently, sorafenib is the only systemic therapy capable of increasing overall survival of hepatocellular carcinoma patients. Unfortunately, its side effects, particularly its overall toxicity, limit the therapeutic response that can be achieved. Superparamagnetic iron oxide nanoparticles （SPIONs） are very attractive for drug delivery because they can be targeted to specific sites in the body through application of a magnetic field, thus improving intratumoral accumulation and reducing adverse effects. Here, nanoformulations based on polyethylene glycol modified phospholipid micelles, loaded with both SPIONs and sorafenib, were successfully prepared and thoroughly investigated by complementary techniques. This nanovector system provided effective drug delivery, had an average hydrodynamic diameter of about 125 nm, had good stability in aqueous medium, and allowed controlled drug loading. Magnetic analysis allowed accurate determination of the amount of SPIONs embedded in each micelle. An in vitro system was designed to test whether the SPION micelles can be efficiently held using a magnetic field under typical flow conditions found in the human liver. Human hepatocellular carcinoma （HepG2） cells were selected as an in vitro system to evaluate tumor cell targeting efficacy of the superparamagnetic micelles loaded with sorafenib. These experiments demonstrated that this delivery platform is able to enhance sorafenib＇s antitumor effectiveness by magnetic targeting. The magnetic nanovectors described here represent promising candidates for targeting specific hepatic tumor sites, where selective release of sorafenib can improve its efficacy and safety profile.

Fabrication of a Magnetite Nanoparticle-loaded Polymeric Nanoplatform for Magnetically Guided Drug Delivery

We developed a magnetite nanoparticle-loaded polymeric nanoplatform for magnetically guided 10- hydroxycamptothecin（HCPT） delivery. The nanoplatform was fabricated by simultaneously incorporating magnetite nanoparticles（NPs） and HCPT into the polymer micelle self-assembled from methoxy polyethylene glycolpoly（D,L-lactide-co-glycolide）（MPEG-PLGA） copolymer. Successful loading of HCPT into the nanoplatform was confirmed by Fourier transform infrared（FTIR） spectroscopy. Subsequently, we examined the in vitro antitumor efficacy of free HCPT and nanoplatform against three different cancer cell lines HeLa, A549 and HepG2. Flow cytometric analysis was condkt ,ucted to reveal the cell apoptosis caused by free HCPT and nanoplatform. Finally, the magnetic targeting property of the nanoplatform was evaluated by a self-designed in vitro experiment.

Possibilities and impossibilities of magnetic nanoparticle use in the control of infectious biofilms

Targeting of chemotherapeutics towards a tumor site by magnetic nanocarriers is considered promising in tumor-control.Magnetic nanoparticles are also considered for use in infection-control as a new means to prevent antimicrobial resistance from becoming the number one cause of death by the year 2050.To this end,magnetic nanoparticles can either be loaded with an antimicrobial for use as a delivery vehicle or modified to acquire intrinsic antimicrobial properties.Magnetic nanoparticles can also be used for the local generation of heat to kill infectious microorganisms.Although appealing for tumor-and infectioncontrol,injection in the blood circulation may yield reticuloendothelial uptake and physical obstruction in organs that yield reduced targeting efficiency.This can be prevented with suitable surface modification.However,precise techniques to direct magnetic nanoparticles towards a target site are lacking.The problem of precise targeting is aggravated in infection-control due to the micrometer-size of infectious biofilms,as opposed to targeting of nanoparticles towards centimeter-sized tumors.This review aims to identify possibilities and impossibilities of magnetic targeting of nanoparticles for infection-control.We first review targeting techniques and the spatial resolution they can achieve as well as surface-chemical modifications of magnetic nanoparticles to enhance their targeting efficiency and antimicrobial efficacy.It is concluded that targeting problems encountered in tumor-control using magnetic nanoparticles,are neglected in most studies on their potential application in infection-control.Currently biofilm targeting by smart,self-adaptive and pH-responsive,antimicrobial nanocarriers for instance,seems easier to achieve than magnetic targeting.This leads to the conclusion that magnetic targeting of nanoparticles for the control of micrometer-sized infectious biofilms may be less promising than initially expected.However,using propulsion rather than precise targeting of magnetic nanoparticles in a magnetic field to traverse through infectious-biofilms can create artificial channels for enhanced antibiotic transport.This is identified as a more feasible,innovative application of magnetic nanoparticles in infection-control than precise targeting and distribution of magnetic nanoparticles over the depth of a biofilm.

Epidermal growth factor receptor-targeted ultra-small superparamagnetic iron oxide particles for magnetic resonance molecular imaging of lung cancer cells in vitro

Background Magnetic resonance （MR） molecular imaging can detect abnormalities associated with disease at the level of cell and molecule. The epidermal growth factor receptor （EGFR） plays an important role in the development of lung cancer. This study aimed to explore new MR molecular imaging targeting of the EGFR on lung cancer cells. Methods We attached ultra-small superparamagnetic iron oxide （USPIO） particles to cetuximab （C225） anti-human IgG using the carbodiimide method. We made the molecular MR contrast agents C225-USPIO and IgG-USPIO, the latter as a control reagent, and determined concentrations according to the Fe content. Lung cancer A549 cells were cultured and immunocytochemistry （SP） was used to detect the expression of EGFR on cells. We detected the binding rate of C225-USPIO to A549 cells with immunofluorescence staining and flow cytometry. We cultured A549 cells with C225-USPIO at a Fe concentration of 50 pg/ml and assayed the binding of C225-USPIO after 1 hour with Prussian blue staining and transmission electron microscopy （TEM）. We determined the effects on imaging of the contrast agent targeted to cells using a 4.7T MRI. We did scanning on the cells labeled with C225-USPIO, IgG-USPIO, and distilled water, respectively. The scanning sequences included axial T1WI, T2WI. Results Immunocytochemical detection of lung cancer A549 cells found them positive for EGFR expression. Immunofluorescence staining and flow cytometry after cultivation with different concentrations of C225-USPIO showed the binding rate higher than the control. Prussian blue staining and transmission electron microscopy revealed that in the C225-USPIO contrast agent group of cells the particle content of Fe in cytoplasmic vesicles or on surface was more than that in the control group. The 4.7T MR imaging （MRI） scan revealed the T2WI signal in the C225-USPIO group of cells decreased significantly more than in unlabeled cells, but there was no significant difference between the time gradients. Conclusions We successfully constructed the molecular imaging agent C225-USPIO targeting the EGFR of A549 lung cancer cells. The imaging agent showed good targeting effect and specificity, and reduced MRI T2 value significantly, thus such molecular contrast agents could provide a new way to measure EGFR levels.

Progress in cancer therapy with functionalized Fe_(3)O_(4) nanomaterials

Malignant neoplasms represent a significant global health threat.To address the need for accurate diagnosis and effective treatment,research is underway to develop therapeutic nanoplatforms.Iron oxide nanoparticles(NPs),specifically Fe_(3)O_(4) NPs have been extensively studied as potential therapeutic agents for cancer due to their unique properties including magnetic targeting,favorable biocompatibility,high magnetic response sensitivity,prolonged in vivo circulation time,stable performance,and high self-metabolism.Their ability to be integrated with magnetic hyperthermia,photodynamic therapy,and photothermal therapy has resulted in the widespread use of Fe_(3)O_(4) NPs in cancer diagnosis and treatment,making them a popular choice for such applications.Various methods can be employed to synthesize magnetic Fe_(3)O_(4) NPs,which can then be surface-modified with biocompatible materials or active targeting molecules.Multifunctional systems can be created by combining Fe_(3)O_(4) NPs with polymers.By combining various therapeutic approaches,more effective biomedical materials can be developed.This paper discusses the synthesis of Fe_(3)O_(4) NPs and the latest research advances in Fe_(3)O_(4)-based nanotherapeutic platforms,as well as their applications in the biomedical field.

Versatile graphitic nanozymes for magneto actuated cascade reaction-enhanced treatment of S.mutans biofilms

Pathogenic oral biofilms especially acid-producing ones cause a variety of oral diseases such as dental caries.Given that bacteria are embedded within the biofilms matrix to prevent the penetration of therapeutic drugs,people have explored the applications of nanoparticles to treat oral diseases.However,current nanoparticle-mediated eradication has not achieved the precise treatment of biofilms,and the stabilities of nanoparticles go on strike because of acidic environment leading to poor therapeutic effectiveness.Herein,we design an integrated nanozyme,CoPt@graphene@glucose oxidase(CoPt@G@GOx),which has cascade reaction activity with two-step process.Hydrogen peroxide(H_(2)O_(2))produced through the glucose oxidation by GOx serves as the substrate for peroxidase-mimic CoPt@G to produce highly toxic hydroxyl radical under acidic environment.Compared to the simple mixture of GOx and CoPt@G,CoPt@G@GOx shows around fourfold catalytic effect enhancement.Meanwhile,CoPt@G@GOx can precisely target the location of the biofilms,which ensures the minimal impact on normal softtissues.Relying on the advantage of the magneto-actuated cascade catalytic activity,CoPt@G@GOx reveals a superior antibacterial ability in the Streptococcus mutans biofilms model.Thus,our results provide an easy and effective method to exploit bifunctional nanozyme as a novel topical agent to prevent the prevalent biofilm-induced oral disease.