磁性水凝胶作为药物载体的应用研究进展

磁性水凝胶是一类同时具有磁性材料、高分子材料及水凝胶的性质特点的无机/有机复合材料。因具有优良的磁学性能及生物相容性,其作为新一代的药物载体可以实现磁响应、磁靶向及磁热疗等功能,在药物控制释放领域具有广阔的应用前景。对磁性水凝胶的制备方法及其在药物载体领域的研究情况进行了综述,详细介绍了磁性水凝胶作为药物载体的两种药物释放机理(ON/OFF模型及热敏释放原理),及其在磁靶向药物控释、磁热疗和磁共振成像方面的应用研究现状。     

On‐Chip Magnetic Platform for Single‐Particle Manipulation with Integrated Electrical Feedback

Methods for the manipulation of single magnetic particles have become very interesting, in particular for in vitro biological studies. Most of these studies require an external microscope to provide the operator with feedback for controlling the particle motion, thus preventing the use of magnetic particles in high‐throughput experiments. In this paper, a simple and compact system with integrated electrical feedback is presented, implementing in the very same device both the manipulation and detection of the transit of single particles. The proposed platform is based on zig‐zag shaped magnetic nanostructures, where transverse magnetic domain walls are pinned at the corners and attract magnetic particles in suspension. By applying suitable external magnetic fields, the domain walls move to the nearest corner, thus causing the step by step displacement of the particles along the nanostructure. The very same structure is also employed for detecting the bead transit. Indeed, the presence of the magnetic particle in suspension over the domain wall affects the depinning field required for its displacement. This characteristic field can be monitored through anisotropic magnetoresistance measurements, thus implementing an integrated electrical feedback of the bead transit. In particular, the individual manipulation and detection of single 1‐μm sized beads is demonstrated.     

Improving the Sensitivity of Fluorescence‐Based Immunoassays by Photobleaching the Autofluorescence of Magnetic Beads

In fluorescence‐based assays, usually a target molecule is captured using a probe conjugated to a capture surface, and then detected using a second fluorescently labeled probe. One of the most common capture surfaces is a magnetic bead. However, magnetic beads exhibit strong autofluorescence, which often overlaps with the emission of the reporter fluorescent dyes and limits the analytical performance of the assay. Here, several widely used magnetic beads are photobleached and their autofluorescence is reduced to 1% of the initial value. Their autofluorescence properties, including their photobleaching decay rates and autofluorescence spectra pre‐ and post‐photobleaching, and the stability of the photobleaching over a period of two months are analyzed. The photobleached beads are stable over time and their surface functionality is retained. In a high‐sensitivity LX‐200 system using photobleached magnetic beads, human interleukin‐8 is detected with a threefold improvement in detection limit and signal‐to‐noise ratio over results achievable with nonbleached beads. Since many contemporary immunoassays rely on magnetic beads as capture surfaces, prebleaching the beads may significantly improve the analytical performance of these assays. Moreover, nonmagnetic beads with low autofluorescence are also successfully photobleached, suggesting that photobleaching can be applied to various capture surfaces used in fluorescence‐based assays.     

Magnetic Suspension Array Technology: Controlled Synthesis and Screening in Microfluidic Networks

Information tagging and processing are vital in information‐intensive applications, e.g., telecommunication and high‐throughput drug screening. Magnetic suspension array technology may offer intrinsic advantages to screening applications by enabling high distinguishability, the ease of code generation, and the feasibility of fast code readout, though the practical applicability of magnetic suspension array technology remains hampered by the lack of quality administration of encoded microcarriers. Here, a logic‐controlled microfluidic system enabling controlled synthesis of magnetic suspension arrays in multiphase flow networks is realized. The smart and compact system offers a practical solution for the quality administration and screening of encoded magnetic microcarriers and addresses the universal need of process control for synthesis in microfluidic networks, i.e., on‐demand creation of droplet templates for high information capacity. The demonstration of magnetic suspension array technology enabled by magnetic in‐flow cytometry opens the avenue toward point‐of‐care multiplexed bead‐based assays, clinical diagnostics, and drug discovery.     

Magnetic Structure Determinations at NBS/NIST

Magnetic neutron scattering plays a central role in determining and understanding the microscopic properties of a vast variety of magnetic systems, from the fundamental nature, symmetry, and dynamics of magnetically ordered materials to elucidating the magnetic characteristics essential in technological applications. From the early days of neutron scattering measurements at NBS/NIST, magnetic diffraction studies have been a central theme involving many universities, industrial and government labs from around the United States and worldwide. Such measurements have been used to determine the spatial arrangement and directions of the atomic magnetic moments, the atomic magnetization density of the individual atoms in the material, and the value of the ordered moments as a function of thermodynamic parameters such as temperature, pressure, and applied magnetic field. These types of measurements have been carried out on single crystals, powders, thin films, and artificially grown multilayers, and often the information collected can be obtained by no other experimental technique. This article presents, in an historical perspective, a few examples of work carried out at the NIST Center for Neutron Research (NCNR), and discusses the key role that the Center can expect to play in future magnetism research.     

磁性纳米颗粒介导的电磁神经治疗的最新进展

目的 介绍磁性纳米颗粒的性质和生物医学应用,以及通过磁性纳米颗粒介导的电磁神经刺激治疗的最新进展.为今后优化刺激参数、提高磁神经刺激效率提供参考.方法 总结近年来国内外对磁性纳米颗粒的研究进展,并重点分析基于磁性纳米颗粒的神经磁刺激方法及效果.结果 磁性纳米颗粒具有成像、靶向给药、磁热疗等生物医学应用,以磁性纳米颗粒为基础进行神经磁刺激的类型可分为磁热刺激、磁电刺激及磁机械力刺激三种.这种刺激方式安全、高效且精准性高,能够改善传统磁刺激方式的缺陷.结论 磁性纳米颗粒性质独特,是近年来研究最多、发展速度最快的纳米材料之一.利用磁性纳米颗粒介导的神经磁刺激具有广阔的应用前景.     

生物高分子磁性微球的研究进展

磁性高分子微球是近二十年来研究的一类新型功能材料。拟从生物高分子磁性微球的制备、结构、性能和应用等几个方面综述近年来国内外有关磁性高分子微球的研究状况。     

Magnetic Multilayers

Magnetic multilayers are artificially structured materials made of ultrathin films of two different mate-rials,alternately ferromagnetic and non-ferromagnetic.They exhibit new magnetic properties differ-ent from those of bulk materials.We review the magnetic properties of metallic magnetic multilayersand focus on interface magnetic anisotropy,giant magnetoresistance and interlayer couplings,whichare of great promise for applications to high density magnetic storage.     

Towards Single Biomolecule Imaging via Optical Nanoscale Magnetic Resonance Imaging

Nuclear magnetic resonance (NMR) spectroscopy is a physical marvel in which electromagnetic radiation is charged and discharged by nuclei in a magnetic field. In conventional NMR, the specific nuclei resonance frequency depends on the strength of the magnetic field and the magnetic properties of the isotope of the atoms. NMR is routinely utilized in clinical tests by converting nuclear spectroscopy in magnetic resonance imaging (MRI) and providing 3D, noninvasive biological imaging. While this technique has revolutionized biomedical science, measuring the magnetic resonance spectrum of single biomolecules is still an intangible aspiration, due to MRI resolution being limited to tens of micrometers. MRI and NMR have, however, recently greatly advanced, with many breakthroughs in nano‐NMR and nano‐MRI spurred by using spin sensors based on an atomic impurities in diamond. These techniques rely on magnetic dipole–dipole interactions rather than inductive detection. Here, novel nano‐MRI methods based on nitrogen vacancy centers in diamond are highlighted, that provide a solution to the imaging of single biomolecules with nanoscale resolution in‐vivo and in ambient conditions.     

生物医学诊疗用磁性微纳材料

磁性微气泡是由包膜微气泡和磁性纳米粒子组成的微纳复合结构,由于其具有超声对比剂和核磁共振对比剂的双重特性,已被应用于双模造影领域。声致穿孔现象（Sonoporation）使得磁性微气泡能介导多种生物学效应,使其在药物输运和基因转染等方面有潜在的应用价值,而磁性微气泡与各种生物分子（抗体、肿瘤标记物等）的偶联,又扩展了磁性微气泡的应用领域,可用于分子影像诊断和靶向治疗肿瘤等方面,可以说磁性微气泡是新一代的生物医学诊疗用磁性微纳材料。总结了磁性微气泡的制备方法,磁性纳米颗粒与微气泡的结合方式,磁性微气泡的功能扩展,以及磁性微气泡在生物医学诊疗领域的实验研究,最后对磁性微气泡在未来的发展方向提出了一些构想,展望了磁性微气泡在诊疗学上广阔的应用前景。     

Optimization of Pathogen Capture in Flowing Fluids with Magnetic Nanoparticles

Magnetic nanoparticles have been employed to capture pathogens for many biological applications; however, optimal particle sizes have been determined empirically in specific capturing protocols. Here, a theoretical model that simulates capture of bacteria is described and used to calculate bacterial collision frequencies and magnetophoretic properties for a range of particle sizes. The model predicts that particles with a diameter of 460 nm should produce optimal separation of bacteria in buffer flowing at 1 L h⁻¹. Validating the predictive power of the model, Staphylococcus aureus is separated from buffer and blood flowing through magnetic capture devices using six different sizes of magnetic particles. Experimental magnetic separation in buffer conditions confirms that particles with a diameter closest to the predicted optimal particle size provide the most effective capture. Modeling the capturing process in plasma and blood by introducing empirical constants (c_e), which integrate the interfering effects of biological components on the binding kinetics of magnetic beads to bacteria, smaller beads with 50 nm diameters are predicted that exhibit maximum magnetic separation of bacteria from blood and experimentally validated this trend. The predictive power of the model suggests its utility for the future design of magnetic separation for diagnostic and therapeutic applications.     

Tweezing of Magnetic and Non‐Magnetic Objects with Magnetic Fields

Although strong magnetic fields cannot be conveniently “focused” like light, modern microfabrication techniques enable preparation of microstructures with which the field gradients – and resulting magnetic forces – can be localized to very small dimensions. This ability provides the foundation for magnetic tweezers which in their classical variant can address magnetic targets. More recently, the so‐called negative magnetophoretic tweezers have also been developed which enable trapping and manipulations of completely nonmagnetic particles provided that they are suspended in a high‐magnetic‐susceptibility liquid. These two modes of magnetic tweezing are complimentary techniques tailorable for different types of applications. This Progress Report provides the theoretical basis for both modalities and illustrates their specific uses ranging from the manipulation of colloids in 2D and 3D, to trapping of living cells, control of cell function, experiments with single molecules, and more.     

Magnetic bead sensing platform for the detection of proteins

Over the past 5 years, the on-chip detection and manipulation of magnetic beads via magnetoelectronics has emerged as a promising new biosensor platform. Magnetic bead sensing (MBS) provides a highly sensitive and specific technique, enabling these sensors to meet the diagnostic needs that are currently not met by existing technologies. Although many studies have proven the high physical sensitivity of magnetic sensors, the establishment of dose-response curves using MBS is unexplored and their capability to sensitively detect low concentrations of target molecules for diagnostic applications has remained unproven. In this study, we have exploited an alternative MBS concept based on the repositioning of the magnetic beads toward the most sensitive location on the spin valve sensors to allow for highly sensitive immunosensing over a wide range of target concentrations. Furthermore, we present the optimization of the magnetoimmuno assay, i.e., the surface chemistry, the blocking procedure, and the type of magnetic particle, for the highly sensitive and specific detection of S100betabeta, a diagnostic marker for stroke and minor head injury. Finally, a dose-response curve was established that illustrates that our MBS platform can specifically detect S100betabeta down to 27 pg/mL, while maintaining a broad dynamic detection range of approximately 2 decades.     

Magnetic Nanocomposites: Magnetic Nanocomposites with Mesoporous Structures: Synthesis and Applications (Small 4/2011)

Magnetic nanocomposites with well‐defined mesoporous structures, shapes, and tailored properties are of immense scientific and technological interest. This review article is devoted to the progress in the synthesis and applications of magnetic mesoporous materials. The first part briefly reviews various general methods developed for producing magnetic nanoparticles (NPs). The second presents and categorizes the synthesis of magnetic nanocomposites with mesoporous structures. These nanocomposites are broadly categorized into four types: monodisperse magnetic nanocrystals embedded in mesoporous nanospheres, microspheres encapsulating magnetic cores into perpendicularly aligned mesoporous shells, ordered mesoporous materials loaded with magnetic NPs inside the porous channels or cages, and rattle‐type magnetic nanocomposites. The third section reviews the potential applications of the magnetic nanocomposites with mesoporous structures in the areas of heath care, catalysis, and environmental separation. The final section offers a summary and future perspectives on the state‐of‐the art in this area.     

Magnetic Nanomaterials for Advanced Regenerative Medicine: The Promise and Challenges

The recent emergence of numerous nanotechnologies is expected to facilitate the development of regenerative medicine, which is a tissue regeneration technique based on the replacement/repair of diseased tissue or organs to restore the function of lost, damaged, and aging cells in the human body. In particular, the unique magnetic properties and specific dimensions of magnetic nanomaterials make them promising innovative components capable of significantly advancing the field of tissue regeneration. Their potential applications in tissue regeneration are the focus here, beginning with the fundamentals of magnetic nanomaterials. How nanomaterials—both those that are intrinsically magnetic and those that respond to an externally applied magnetic field—can enhance the efficiency of tissue regeneration is also described. Applications including magnetically controlled cargo delivery and release, real‐time visualization and tracking of transplanted cells, magnetic regulation of cell proliferation/differentiation, and magnetic activation of targeted ion channels and signal pathways involved in regeneration are highlighted, and comments on the perspectives and challenges in magnetic nanomaterial‐based tissue regeneration are given.     

Synthesis,Functionalization, and Biomedical Applications of Multifunctional Magnetic Nanoparticles

Synthesis of multifunctional magnetic nanoparticles (MFMNPs) is one of the most active research areas in advanced materials. MFMNPs that have magnetic properties and other functionalities have been demonstrated to show great promise as multimodality imaging probes. Their multifunctional surfaces also allow rational conjugations of biological and drug molecules, making it possible to achieve target‐specific diagnostics and therapeutics. This review first outlines the synthesis of MNPs of metal oxides and alloys and then focuses on recent developments in the fabrication of MFMNPs of core/shell, dumbbell, and composite hybrid type. It also summarizes the general strategies applied for NP surface functionalization. The review further highlights some exciting examples of these MFMNPs for multimodality imaging and for target‐specific drug/gene delivery applications.     

Preparation and control of the formation of single core and clustered nanoparticles for biomedical applications using a versatile amphiphilic diblock copolymer

We report the application of a versatile diblock copolymer, poly(ethylene oxide)-b-poly(γ-methacryloxypropyl trimethoxysilane) (PEO-b-PγMPS), to prepare nanocrystals such as iron oxide nanoparticles or quantum dots, with either a single core or multi-core cluster, for biomedical applications. This amphiphilic copolymer comprises both a hydrophilic PEO segment and a hydrophobic segment with a “surface anchoring moiety” (the silane group) which can interact effectively with the hydrophobic nanocrystals through ligand exchange. One of the unique features of this work is that we can control the formation of either single core nanoparticles or multi-core nanoclusters by simply varying the conditions of ligand exchange and aging of the mixture of block copolymer and nanoparticles without needing to change the copolymer. The morphologies of the resulting single core nanoparticles or multi-core nanoclusters were confirmed by dynamic light scattering and transmission electron microscopy. The clustered nanoparticles exhibit enhanced physicochemical properties that are beyond those expected from a simple accumulation of individual nanoparticles. Additionally, the hybrid nanoparticles containing both magnetic iron oxide nanoparticles and optical quantum dots obtained using our strategy provide have combined magnetic and optical functionalities that allow for potential new and expanded biomedical applications, as demonstrated by their use for magnetic resonance imaging and biomarker-targeted cell imaging.     

Quantitative Magnetic Separation of Particles and Cells Using Gradient Magnetic Ratcheting

Extraction of rare target cells from biosamples is enabling for life science research. Traditional rare cell separation techniques, such as magnetic activated cell sorting, are robust but perform coarse, qualitative separations based on surface antigen expression. A quantitative magnetic separation technology is reported using high‐force magnetic ratcheting over arrays of magnetically soft micropillars with gradient spacing, and the system is used to separate and concentrate magnetic beads based on iron oxide content (IOC) and cells based on surface expression. The system consists of a microchip of permalloy micropillar arrays with increasing lateral pitch and a mechatronic device to generate a cycling magnetic field. Particles with higher IOC separate and equilibrate along the miropillar array at larger pitches. A semi‐analytical model is developed that predicts behavior for particles and cells. Using the system, LNCaP cells are separated based on the bound quantity of 1 μm anti‐epithelial cell adhesion molecule (EpCAM) particles as a metric for expression. The ratcheting cytometry system is able to resolve a ±13 bound particle differential, successfully distinguishing LNCaP from PC3 populations based on EpCAM expression, correlating with flow cytometry analysis. As a proof‐of‐concept, EpCAM‐labeled cells from patient blood are isolated with 74% purity, demonstrating potential toward a quantitative magnetic separation instrument.     

Drug/Dye‐Loaded,Multifunctional Iron Oxide Nanoparticles for Combined Targeted Cancer Therapy and Dual Optical/Magnetic Resonance Imaging

A biocompatible, multimodal, and theranostic functional iron oxide nanoparticle is synthesized using a novel water‐based method and exerts excellent properties for targeted cancer therapy, and optical and magnetic resonance imaging. For the first time, a facile, modified solvent diffusion method is used for the co‐encapsulation of both an anticancer drug and near‐infrared dyes. The resulting folate‐derivatized theranostics nanoparticles could allow for targeted optical/magnetic resonance imaging and targeted killing of folate‐expressing cancer cells.     

镀银磁性PMMA微球的制备

采用化学镀法制得了表面包覆银层的导电磁性聚甲基丙烯酸甲酯(PMMA)微球。对粗糙度不同的微球进行镀银,研究了银在微球上的沉积机理。表面改性使磁性PMMA微球功能化,具有和银强烈结合的能力,从而得到包覆均匀的导电磁性微球。研究了硝酸银和磁性微球的含量对包覆效果及导电性能的影响,并通过SEM和EDS对镀银磁性微球的表面形貌及组成进行了分析。