Surface modification of magnetic nanoparticles in biomedicine

Progress in surface modification of magnetic nanoparticles(MNPs)is summarized with regard to organic molecules,macromolecules and inorganic materials.Many researchers are now devoted to synthesizing new types of multi-functional MNPs,which show great application potential in both diagnosis and treatment of disease.By employing an ever-greater variety of surface modification techniques,MNPs can satisfy more and more of the demands of medical practice in areas like magnetic resonance imaging(MRI),fluorescent marking,cell targeting,and drug delivery.     

Second harmonic magnetoacoustic responses of magnetic nanoparticles in magnetoacoustic tomography with magnetic induction

Due to the unique magnetic, mechanical and thermal properties, magnetic nanoparticles(MNPs) have comprehensive applications as the contrast and therapeutic agents in biomedical imaging and magnetic hyperthermia. The linear and nonlinear magnetoacoustic responses determined by the magnetic properties of MNPs have attracted more and more attention in biomedical engineering. By considering the relaxation time of MNPs, we derive the formulae of second harmonic magnetoacoustic responses(2H-MARs) for a cylindrical MNP solution model based on the mechanical oscillations of MNPs in magnetoacoustic tomography with magnetic induction(MAT-MI). It is proved that only the second harmonic magnetoacoustic oscillations can be generated by MNPs under an alternating magnetic excitation. The acoustic pressure of the 2H-MAR is proportional to the square of the magnetic field intensity and exhibits a linear increase with the concentration of MNPs. Numerical simulations of the 2H-MAR are confirmed by the experimental measurements for various magnetic field intensities and solution concentrations using a laser vibrometer. The favorable results demonstrate the feasibility of the harmonic measurements without the fundamental interference of the electromagnetic excitation, and suggest a new harmonic imaging strategy of MAT-MI for MNPs with enhanced spatial resolution and improved signal-to-noise ratio in biomedical applications.     

Labelling of cultured macrophages with novel magnetic nanoparticles

Magnetic resonance (MR) imaging is capable of demonstrating human anatomy and pathological conditions. Iron oxide magnetic nanoparticles (MNPs) have been used in MR imaging as liver-specific contrast medium, cellular and molecular imaging probes. Because few studies focused on the MNPs other than iron oxides, we developed FeNi alloy MNPs coated with polyethylenimine (PEI). In this study, we demonstrated PEI-coated FeNi MNPs are able to label the cells, which could be detected in MR imaging. For labelling purpose, MNPs were incubated with mouse macrophage cell line (Raw 264.7) for 24 h and these PEI-labelled FeNi alloy MNPs can be uptaken by macrophages efficiently compared with Ferucarbotran, a commercialized superparamagnetic iron oxide (SPIO) under flow cytometry measurement. Besides, these cells labelled with MNPs could be imaged in MR with the identical potency as Ferucarbotran. Further investigation of the cells using Prussian blue staining revealed that FeNi alloy MNPs inside the cells is not oxidized. This phenomenon alleviated the consideration of potential risk of nickel toxicity. We conclude that PEI-coated FeNi MNPs could be candidate for MR contrast medium.     

Using magnetic nanoparticles to manipulate biological objects

The use of magnetic nanoparticles （MNPs） for the manipulation of biological objects, including proteins, genes, cellular organelles, bacteria, cells, and organs, are reviewed. MNPs are popular candidates for controlling and probing biological objects with a magnetic force. In the past decade, progress in the synthesis and surface engineering of MNPs has further enhanced this popularity.     

Cobalt Phosphide Nanoparticles Applied as a Theranostic Agent for Multimodal Imaging and Anticancer Photothermal Therapy

Biocompatible single‐component theranostic nanoagents instinctly affording multiple imaging modalities with satisfying therapeutic functions are highly desirable for anticancer treatments. Although cobalt‐based phosphides are well‐recognized as competent electrocatalysts, their potentials for biomedical applications remain unexplored. In this work, cobalt phosphide nanoparticles (CoP NPs) are developed to be a powerful theranostic agent for multimodal imaging and anticancer photothermal therapy. The uniform CoP NPs in a size of ≈21 nm are synthesized via a facile thermal decomposition method, followed by surface modification. The resultant CoP NPs exhibit excellent compatibility and stability in water as well as various physiological solutions. Supported by the good biocompatibility, strong near‐infrared absorption, and high photothermal conversion property, significant photothermal effect of the NPs is demonstrated, realizing efficient hyperthermia ablation on cancer cells. Importantly, the CoP NPs have shown considerable capabilities on high‐contrast in vitro and in vivo triple‐modal imaging, including infrared thermal (IRT), photoacoustic (PA), and T₂‐weighted magnetic resonance (MR) imaging. This work has unraveled the promising potentials of CoP‐based nanoagent for precise diagnosis and efficient therapy.     

A thermo-fluid analysis in magnetic hyperthermia

In the last years, hyperthermia induced by the heating of magnetic nanoparticles （MNPs） in an alternating magnetic field received considerable attention in cancer therapy. The thermal effects could be automatically controlled by using MNPs with selective magnetic absorption properties. In this paper, we analyze the temperature field determined by the heating of MNPs, injected in a malignant tissue, subjected to an alternating magnetic field. The main parameters which have a strong influence on temperature field are analyzed. The temperature evolution within healthy and tumor tissues are analyzed by finite element method （FEM） simulations in a thermo-fluid model. The cooling effect produced by blood flow in blood vessels from the tumor is considered. A thermal analysis is conducted under different distributions of MNP injection sites. The interdependence between the optimum dose of the nanoparticles and various types of tumors is investigated in order to understand their thermal effect on hyperthermia therapy. The control of the temperature field in the tumor and healthy tissues is an important step in the healing treatment.     

基于图像质量评价的手术机器人系统磁共振兼容性分析方法

为保证手术安全及操作精度,基于磁共振图像导航的手术机器人系统需具备磁共振设备兼容性. 针对这一问题,本文提出了基于磁共振图像质量评价的手术机器人系统磁共振设备兼容性分析方法,扩展了图像数据集,并结合图像信噪比、图像变化因数、磁共振图像畸变量等评价参数,逐一分析机器人系统组件通电、机器人系统运动对磁共振图像质量产生的影响,建立图像质量评价依据. 实验结果表明,该质量评价方法可充分分析手术机器人及其系统组件的磁共振兼容性,且可为医疗手术机器人系统组件的磁共振兼容性分析提供测试方法与理论依据.     

Magnetic nanoparticle-based cancer therapy

Nanoparticles(NPs) with easily modified surfaces have been playing an important role in biomedicine.As cancer is one of the major causes of death,tremendous efforts have been devoted to advance the methods of cancer diagnosis and therapy.Recently,magnetic nanoparticles(MNPs) that are responsive to a magnetic field have shown great promise in cancer therapy.Compared with traditional cancer therapy,magnetic field triggered therapeutic approaches can treat cancer in an unconventional but more effective and safer way.In this review,we will discuss the recent progress in cancer therapies based on MNPs,mainly including magnetic hyperthermia,magnetic specific targeting,magnetically controlled drug delivery,magnetofection,and magnetic switches for controlling cell fate.Some recently developed strategies such as magnetic resonance imaging(MRI) monitoring cancer therapy and magnetic tissue engineering are also addressed.     

Atomic force microscopy and transmission electron microscopy of biocompatible magnetic fluids: A comparative analysis

The present study provides a comparative analysis of the size dispersity of magnetic nanoparticles (MNPs) within magnetic fluids as obtained from atomic force microscopy (AFM) and transmission electron microscopy (TEM). Whereas the mean particle diameter obtained from the AFM data presented a reduction of about 34% as compared to the value obtained from the TEM data, the standard deviation obtained from the AFM data is twice the value found from the TEM data. Similarities and differences in the size dispersity parameters are discussed in terms of sample preparation and tip characteristics. A two-dimensional mode for the deposition of the MNPs on top of the mica substrate is discussed as well.     

Highly hydrated poly(allylamine)/silica magnetic resin

The creation of multifunctional nanomaterials by combining organic and inorganic components is a growing trend in nanoscience. The unique size-dependent properties of magnetic nanoparticles (MNPs) make them amenable to numerous applications such as carriers of expensive biological catalysts, in magnetically assisted chemical separation of heavy metals and radionuclides from contaminated water sources. The separation of minor actinides from high-level radionuclide waste requires a sorbent stable in acidic pH, with ease of surface functionalization, and a high capacity for binding the molecules of interest. For the described experiments, the MNPs with 50 nm average size were used (size distribution from 20 to 100 nm and an iron content of 80–90 w/w%). The MNPs that have been double coated with an initial silica coating for protection against iron solubilization and oxidation in nitric acid solution (pH 1) and a second silica/polymer composite coating incorporating partially imbedded poly(allylamine) (PA). The final product is magnetic, highly swelling, containing >95% water, with >0.5 mmol amines g^?1 available for functionalization. The amine groups of the magnetic resin were functionalized with the chelating molecules diethylenetriaminepentaacetic acid (DTPA) and N,N-dimethyl-3-oxa-glutaramic acid (DMOGA) for separation of minor actinides from used nuclear fuel.     

超极化~(129)Xe磁共振波谱和成像及在生物医学中的应用

文章简要介绍了磁共振波谱和成像的基本原理和对限制其灵敏度的挑战,详细阐述了为增强磁共振信号而制备超极化129Xe的物理机制,论述了129Xe在生物组织中的溶解性以及化学位移的特异性,综述了当前超极化129Xe在肺部、脑部成像领域的研究进展和在临床方面应用所取得的有代表性的研究成果,并讨论了基于超极化129Xe分子生物探针的超灵敏磁共振技术的研究前景,最后对超极化129Xe在生物医学领域的应用与发展作了展望.     

Investigations and Modeling of the Effect of Magnetic Nanoparticles on MR Image Contrast

The investigations of nuclear magnetic resonance (NMR) relaxation of protons in aqueous solution and 2% agar–agar gel in the presence of magnetic nanoparticles were performed. To identify the effect of magnetic nanoparticles on the contrast of magnetic resonance images, the dependences of the MR signal intensity on the parameters of the two pulse radio-frequency (RF) sequences (spin-echo, gradient-echo) most commonly used in MRI for different values of the magnetic nanoparticle (MNP) concentration were simulated and analyzed. Recommendations for choosing the optimal values of pulse RF sequence parameters for MR imaging (MRI) in the presence of MNPs are formulated. MRI studies of phantom samples with 2% agar–agar gel containing MNPs have been performed for choosing the fast pulse RF sequence which shows the greatest contrast effect on MR images. A program for modeling magnetic resonance tomograms and determination of optimal values of pulse RF sequence parameters to achieve the best contrast of magnetic resonance images is developed. This program allows to reduce the time of MRI studies, to assess the possibility of using MNPs for contrast of MR images and to simulate the MR image in the presence of magnetic nanoparticles at the planning stage of procedures in MR-guided theranostics.     

Imaging the Magnetic Reversal of Isolated and Organized Molecular‐Based Nanoparticles using Magnetic Force Microscopy

In the race towards miniaturization in nanoelectronics, magnetic nanoparticles (MNPs) have emerged as potential candidates for their integration in ultrahigh‐density recording media. Molecular‐based materials open the possibility to design new tailor‐made MNPs with variable composition and sizes, which benefit from the intrinsic properties of these materials. Before their implementation in real devices is reached, a precise organization on surfaces and a reliable characterization and manipulation of their individual magnetic behavior are required. In this paper, it is demonstrated how molecular‐based MNPs are accurately organized on surfaces and how the magnetic properties of the individual MNPs are detected and tuned by means of low‐temperature magnetic force microscopy (LT‐MFM) with variable magnetic field. The magnetization reversal on isolated and organized MNPs is investigated; in addition, the temperature dependence of their magnetic response is evaluated.     

Simulating the effects of time-varying magnetic fields with a realistic simulated scanner

Transient magnetic fields induce changes in magnetic resonance (MR) images ranging from small, visually undetectable effects (caused, for instance, by neuronal currents) to more significant ones, such as those created by the gradient fields and eddy currents. Accurately simulating these effects may assist in correcting or optimising MR imaging for many applications (e.g., diffusion imaging, current density imaging, use of magnetic contrast agents, neuronal current imaging, etc.). Here we have extended an existing MR simulator (POSSUM) with a model for changing magnetic fields at a very high-resolution time-scale. This simulator captures a realistic range of scanner and physiological artifacts by modeling the scanner environment, pulse sequence details and subject properties (e.g., brain geometry and air-tissue boundaries).     

Formation of multifunctional Fe_3O_4/Au composite nanoparticles for dual-mode MR/CT imaging applications

Recent advances with iron oxide/gold(Fe3O4/Au) composite nanoparticles(CNPs) in dual-modality magnetic resonance(MR) and computed tomography(CT) imaging applications are reviewed. The synthesis and assembly of "dumbbelllike" and "core/shell" Fe3O4/Au CNPs is introduced. Potential applications of some developed Fe3O4/Au CNPs as contrast agents for dual-mode MR/CT imaging applications are described in detail.     

A novel radio frequency coil for veterinary magnetic resonance imaging system

In this article,a novel designed radio frequency (RF) coil is designed and built for the imaging of puppies in a V-shape permanent magnetic resonance imaging (MRI) system.Two sets of Helmholtz coil pairs with a V-shape structure are used to improve the holding of an animal in the coil.The homogeneity and the sensitivity of the RF field in the coil are analysed by theoretical calculation.The size and the shape of the new coil are optimized and validated by simulation through using the finite element method (FEM).Good magnetic resonance (MR) images are achieved on a shepherd dog.     

Functionalized magnetic nanoparticles for drug delivery in tumor therapy

The side effects of chemotherapy are mainly the poor control of drug release. Magnetic nanoparticles(MNPs) have super-paramagnetic behaviors which are preferred for biomedical applications such as in targeted drug delivery, besides, in magnetic recording, catalysis, and others. MNPs, due to high magnetization response, can be manipulated by the external magnetic fields to penetrate directly into the tumor, thus they can act as ideal drug carriers. MNPs also play a crucial role in drug delivery system because of their high surface-to-volume ratio and porosity. The drug delivery in tumor therapy is related to the sizes, shapes, and surface coatings of MNPs as carriers. Therefore, in this review, we first summarize the effects of the sizes, shapes, and surface coatings of MNPs on drug delivery, then discuss three types of drug release systems, i.e., p H-controlled, temperature-controlled, and magnetic-controlled drug release systems, and finally compare the principle of passive drug release with that of active drug release in tumor therapy.     

Agglomeration,colloidal stability,and magnetic separation of magnetic nanoparticles: collective influences on environmental engineering applications

Magnetic nanoparticles (MNPs) which exhibit magnetic and catalytic bifunctionalities have been widely accepted as one of the most promising nanoagents used in water purification processes. However, due to the magnetic dipole-dipole interaction, MNPs can easily lose their colloidal stability and tend to agglomerate. Thus, it is necessary to enhance their colloidal stability in order to maintain the desired high specific surface area. Meanwhile, in order to successfully utilize MNPs for environmental engineering applications, an effective magnetic separation technology has to be developed. This step is to ensure the MNPs that have been used for pollutant removal can be fully reharvested back. Unfortunately, it was recently highlighted that there exists a conflicting role between colloidal stability and magnetic separability of the MNPs, whereby the more colloidally stable the particle is, the harder for it to be magnetically separated. In other words, attaining a win-win scenario in which the MNPs possess both good colloidal stability and fast magnetic separation rate becomes challenging. Such phenomenon has to be thoroughly understood as the colloidal stability and the magnetic separability of MNPs play a pivotal role on affecting their effective implementation in water purification processes. Accordingly, it is the aim of this paper to provide reviews on (i) the colloidal stability and (ii) the magnetic separation of MNPs, as well as to provide insights on (iii) their conflicting relationship based on recent research findings.

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Graphical abstract Interrelationship of agglomeration, colloidal stability, and magnetic separability of nanoparticles

     

Mesoporous Silica Promoted Deposition of Bioinspired Polydopamine onto Contrast Agent: A Universal Strategy to Achieve Both Biocompatibility and Multiple Scale Molecular Imaging

Polydopamine (PDA) preserves universal coating and metal‐binding ability, and is suitable for application in synthesizing multifunctional agents. Herein, utilizing mesoporous silica assisted deposition to enhance both heterogeneous nucleation and loading amounts of PDA, the magnetic resonance (MR) T₁ component (PDA‐Fe³⁺) and MR T₂/computed tomography (CT)/multiphoton luminescence (MPL) component (FePt) have been successfully integrated in aqueous solution. This four‐in‐one (T₁, T₂, CT, MPL) imaging nanocomposite, FePt@mSiO₂ @PDA‐polyethylene glycol (PEG), demonstrated its multi‐imaging power both in vitro/in vivo. According to our in vitro/in vivo results, FePt@mSiO₂@PDA‐PEG reveals water‐content‐dependent property in T₁ MR imaging, which suggests the necessity of having dual‐modal MR ability in a single particle for the precision diagnosis. Most importantly, this dual (T₁,T₂)‐MRI/CT contrast agent is demonstrated complementary to each other in the in vivo testing. PDA coated mesoporous silica also offers an advantage of delayed degradation that prevents adverse effects caused by silica fragments before excretion. The potential of this nanocomposites in both drug carrier and photothermal agent was further evaluated by using doxorubicin and monitoring solution temperature after irradiating 808 nm continuous‐wave, respectively The merits of controlled polymerization, enhanced PDA loading, and biofavorable degradation make this methodology promising to other nanoparticle@mSiO₂ for a wide range of bioapplications.     

Uptake of magnetic nanoparticles into cells for cell tracking

A challenge for future applications in nanotechnology is the functional integration of nano-sized materials into cellular structures. Here we investigated superparamagnetic Fe₃O₄ iron oxide nanoparticles coated with a lipid bilayer for uptake into cells and for targeting subcellular compartments. It was found that magnetic nanoparticles (MNPs) are effectively taken up into cells and make cells acquire magnetic activity. Biotin-conjugated MNPs were further functionalized by binding of the fluorescent tag streptavidin–fluorescein isothiocyanate (FITC) and, following uptake into cells, shown to confer magnetic activity and fluorescence labeling. Such FITC-MNPs were localized in the lysosomal compartment of cells which suggests a receptor-mediated uptake mechanism.