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.     

Quantitative targeting maps based on experimental investigations for a branched tube model in magnetic drug targeting

Magnetic drug targeting (MDT), because of its high targeting efficiency, is a promising approach for tumour treatment. Unwanted side effects are considerably reduced, since the nanoparticles are concentrated within the target region due to the influence of a magnetic field. Nevertheless, understanding the transport phenomena of nanoparticles in an artery system is still challenging. This work presents experimental results for a branched tube model. Quantitative results describe, for example, the net amount of nanoparticles that are targeted towards the chosen region due to the influence of a magnetic field. As a result of measurements, novel drug targeting maps, combining, e.g. the magnetic volume force, the position of the magnet and the net amount of targeted nanoparticles, are presented. The targeting maps are valuable for evaluation and comparison of setups and are also helpful for the design and the optimisation of a magnet system with an appropriate strength and distribution of the field gradient. The maps indicate the danger of accretion within the tube and also show the promising result of magnetic drug targeting that up to 97% of the nanoparticles were successfully targeted.     

Superparamagnetic nanoparticles for biomedical applications: Possibilities and limitations of a new drug delivery system

Nanoparticles can be used in biomedical applications, where they facilitate laboratory diagnostics, or in medical drug targeting. They are used for in vivo applications such as contrast agent for magnetic resonance imaging (MRI), for tumor therapy or cardiovascular disease. Very promising nanoparticles for these applications are superparamagnetic nanoparticles based on a core consisting of iron oxides (SPION) that can be targeted through external magnets. SPION are coated with biocompatible materials and can be functionalized with drugs, proteins or plasmids. In this review, the characteristics and applications of SPION in the biomedical sector are introduced and discussed.     

Boosting Postsurgical Outcomes of Orthotopic Hepatocellular Carcinoma via an EpCAM‐Targeting Theranostic Nanoparticle

Hepatectomy is one of the main treatments for hepatocellular carcinoma (HCC). However, because microscopic tumor residues are often present after surgery, the recurrence rate of HCC remains extremely high. A multimodality imaging‐guided multifunctional nanoparticle, indocyanine‐green–gadolinium–copper sulfide@bovine‐serum‐albumin–epithelial‐cell‐adhesion molecule (EpCAM), is developed for HCC treatment based on a novel theranostic strategy. After intravenous injection of these nanoparticles into HCC‐bearing mice, remarkably selective accumulation and highly efficient retention of the nanoparticles in tumor sites are observed. This is due to the EpCAM's specific targeting ability, which also results in enhanced HCC contrast in a tri‐modal visualization, which unites magnetic resonance, photoacoustic, and fluorescence imaging. Moreover, nanoparticle uptake into the HCC allows photothermal therapy (PTT) as an interoperative adjuvant strategy for further eliminating possible microscopic residues and boosting HCC surgery outcomes. This theranostic strategy not only helps with precise diagnosis of HCC but enables intraoperatively imaging guidance for accurate tumor resection. Moreover, postoperation longitudinal observation demonstrates that intraoperative imaging‐guided resection alongside a PTT‐integrated treatment strategy can result in a significant improvement of overall survival rate. These multifunctional EpCAM‐targeting nanoparticles may respresent a novel theranostic strategy to improve postsurgical HCC treatment.     

Preparation of a biocompatible magnetic film from an aqueous ferrofluid

Very promising nanoparticles for biomedical applications or in medical drug targeting are superparamagnetic nanoparticles based on a core consisting of iron oxides (SPION) that can be targeted through external magnets. Polyvinyl alcohol (PVA) is a unique synthetic biocompatible polymer that can be chemically cross-linked to form a gel. Biotechnology applications of magnetic gels include biosensors, targeted drug delivery, artificial muscles and magnetic buckles. These gels are produced by incorporating magnetic materials in the polymer composites. In this paper we report the synthesis of an aqueous ferrofluid and the preparation of a biocompatible magnetic gel with polyvinyl alcohol and glutharaldehyde (GTA). HClO₄ was used to induce the peptization since this kind of ferrofluid does not have surfactant. The magnetic gel was dried to generate a biocompatible film.     

磁纳米粒子介导的磁致振动超声成像研究现状及展望

超声成像作为临床上常用的影像检测方法,在疾病诊断、术中导航和术后评估等方面发挥重要作用.随着纳米技术的快速发展,不同的微纳米材料或成像探针的构建,为超声成像提供新的发展动力.其中,磁纳米粒子介导的磁致振动超声成像是近年来发展的一种新兴的成像技术.其主要原理是基于磁纳米粒子在变化磁场作用下产生磁致振动,利用超声波探测粒子...     

Theranostic Nanoplatforms for MRSA Detection and Destruction from Whole Blood

Bloodstream infection with methicillin‐resistant Staphylococcus aureus (MRSA) and other drug‐resistant bacteria kill several million people in the world every year. Detection of drug‐resistant bacteria in the blood stream is clinically important to save lives. Driven by this need, multifunctional theranostic nanoplatforms have been developed for simultaneous targeted imaging and multimodal photodestruction of MRSA in a whole‐blood sample. Experimental data for the whole‐blood sample spiked with MRSA show that the theranostic nanoplatform can be used for fluorescence imaging after magnetic separation even in a 10^?5:1 ratio. A targeted photodynamic and photothermal combined treatment shows that the multimodal treatment regime can dramatically enhance the possibility of destroying MRSA in vitro. Therefore, our developed theranostic nanoplatform have a great potential as a fluorescent marker and as a light absorber for combined therapy in clinical settings. The possible mechanisms and operating principles are discussed for targeted imaging and combined therapeutic actions using theranostic nanoplatform.     

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.     

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.     

Experimental investigations on a branched tube model in magnetic drug targeting

Magnetic drug targeting (MDT) has been established as a promising technique for tumour treatment. Due to its high targeting efficiency unwanted side effects are considerably reduced, since drug-loaded nanoparticles are concentrated within a target region due to the influence of a magnetic field. This work presents experimental results that are based on systematic quantitative measurements on a branched tube model as a model system for a blood vessel supplying a tumour. The systematic measurements are summarized in novel drug targeting maps, combining e.g. the net amount of targeted nanoparticles, the magnetic volume force and also the position of the magnet. The model, the injection procedure and the ferrofluid are chosen close to the parameters of a medical application. This will allow transfer of the results to future medical investigations. This work will present a targeting map, where the concentration of the injected ferrofluid is in the range of experiments with an ex vivo bovine artery model.     

A sonochemical route for the encapsulation of drug in magnetic microspheres

This study focused on the preparation and characterization of magnetic targeted antibiotic microspheres (MTAMs). MTAMs were prepared by a sonochemical method in the presence of hydrophobic Fe₃O₄ nanoparticles and tetracycline. The properties of MTAMs were characterized by transmission electron microscopy, Fourier-transform infrared spectrum, thermogravimetric analysis, vibration sample magnetometry, and bacteriostatic experiment. The results indicated that the superparamagnetic microspheres have ultrafine size (below 230 nm), high saturation magnetization (80.90 emu/g), high biocompatibility, biodegradability, controlled-release, and antibiotic effect. It has been proved that MTAMs can carry out the function of magnetic targeted drugs delivery system by putting together magnetic materials and antibiotics. The possible formation mechanism of MTAMs was also discussed. In summary, MTAMs had potential in medical imaging, drug targeting, and catalysis.     

Biochemical and biomedical applications of multifunctional magnetic nanoparticles: a review

Nanotechnology offers tremendous potential for future medical diagnosis and therapy. Various types of nanoparticles have been extensively studied for numerous biochemical and biomedical applications. Magnetic nanoparticles are well-established nanomaterials that offer controlled size, ability to be manipulated by an external magnetic field, and enhancement of contrast in magnetic resonance imaging. As a result, these nanoparticles could have many applications including bacterial detection, protein purification, enzyme immobilization, contamination decorporation, drug delivery, hyperthermia, etc. All these biochemical and biomedical applications require that these nanoparticles should satisfy some prerequisites including high magnetization, good stability, biocompatibility, and biodegradability. Because of the potential benefits of multimodal functionality in biomedical applications, in this account highlights some general strategies to generate magnetic nanoparticle-based multifunctional nanostructures. After these magnetic nanoparticles are conjugated with proper ligands (e.g., nitrilotriacetate), polymers (e.g., polyacrylic acid, chitosan, temperature- and pH-sensitive polymers), antibodies, enzymes, and inorganic metals (e.g., gold), such biofunctional magnetic nanoparticles exhibit many advantages in biomedical applications. In addition, the multifunctional magnetic nanoparticles have been widely applied in biochemical fields including enzyme immobilization and protein purification.     

Targeting Upconversion Nanoprobes for Magnetic Resonance Imaging of Early Colon Cancer

Colon cancer (CC) is one of the most common intestinal malignancies and is difficult to detect in its early stage by magnetic resonance imaging (MRI) with currently used contrast agents (CAs). The development of targeted CAs contributes to the early diagnosis of CC and thereby enables early intervention and timely therapy. Considering the outstanding performance of upconversion nanoprobes (UCNPs) in high‐performance MR and fluorescence imaging, a new type of nanoprobes with considerably enhanced imaging performance is developed herein. Carcinoembryonic antigen (CEA) antibody is conjugated onto the surface of UCNPs to achieve the targeted imaging of early CC tumors, which overexpress CEA. Both toxicity tests and histological/hematological examinations demonstrate the excellent biocompatibility of these CC‐targeting nanoprobes, which possess great potential for clinical application in the early diagnosis of CC.     

Magnetic Fluorescent Composite Nanoparticles for the Fluoroimmunoassays of Newcastle Disease Virus and Avian Virus Arthritis Virus

A new detection format for multiplexed analysis based on the use of magnetic fluorescent composite nanoparticles was presented in this paper. Two different antigens, Newcastle disease virus (NDV) antigen and Avian virus arthritis virus (AVAV) antigen, were conjugated to two kinds of magnetic fluorescent composite nanoparticles of different luminescent colors, while red-emitting CdTe QDs were attached to the antibody of NDV and AVAV. Both CdTe QDs-labeled antibodies and magnetic fluorescent composite nanoparticles labeled antigens were used to form a typical immunoreaction system for the detection of NDV and AVAV. Also a typical mixed separation format was realized, which showed the outstanding magnetic properties of composite nanoparticles and the broad application in immunoseparation.     

Targeted and Specific Modification with 4-Carboxybenzeneboronic Acid and TPGS of Fluorescent Gold Nanoparticles and the Enhanced Antitumor Activity Research

A targeting and specific fluorescent gold nanoparticle is prepared for tracing of drug and effective treatment of cancers. First, 4-carboxybenzeneboronic acid (CBPA) and D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) are used to modify cyclodextrins (CDs), then modified cyclodextrins and polyethylene glycol (PEG) are used to stabilize gold nanoclusters to prepare fluorescent gold nanoparticles (AuNCs@CD-TPGS-CBPA/PEG). CBPA has targeting and TPGS can induce apoptosis, therefore, AuNCs@CD-TPGS-CBPA/PEG has targeting and certain anti-tumor activity. The structure and morphology of the nanomaterial are characterized by using nuclear magnetic resonance (NMR) spectroscopy and transmission electron microscope (TEM). Paclitaxel (PTX) is loaded into the hydrophobic cavity of CDs to form targeting specific drug-loaded fluorescent gold nanoparticles (AuNCs@CD-TPGS-CBPA/PEG/PTX). Biological performances of AuNCs@CD-TPGS-CBPA/PEG are studied by in vitro and in vivo experiments. In vitro test results confirm that AuNCs@CD-TPGS-CBPA/PEG could be internalized by tumor cells, and effectively against tumor cells, but it is biocompatible to normal cells. In vivo experiments prove that AuNCs@CD-TPGS-CBPA/PEG has excellent targeting, biocompatibility, and enhanced antitumor capability, could enrich and stay for a long time in the tumor regions, effectively prolong the lifetime of tumor-bearing mice. Therefore, this work provides an insight into the development of fluorescent gold nanomaterials for practical biomedical application.     

PEG Coated Biocompatible Cadmium Chalcogenide Quantum Dots for Targeted Imaging of Cancer Cells

Cancer stands as a leading cause of mortality worldwide and diagnostics of cancer still faces drawbacks. Optical imaging of cancer would allow early diagnosis, evaluation of disease progression and therapy efficiency. To that aim, we have developed highly biocompatible PEG functionalized cadmium chalcogenide based three differently luminescent quantum dots (QDs) (CdS, CdSe and CdTe). Folate targeting scheme was utilized for targeting cancer cell line, MCF-7. We demonstrate the biocompatibility, specificity and efficiency of our nanotool in detection of cancer cells sparing normal cell lines with retained fluorescence of functionalized QDs as parental counterpart. This is the first time report of utilizing three differently fluorescent QDs and we have detailed about the internalization of these materials and time dependent saturation of targeting schemes. We present here the success of utilizing our biocompatible imaging tool for early diagnosis of cancer.     

In Vivo Targeted Cancer Theranostics by Core/Shell‐Structured Multifunctional Prussian Blue/PLGA “Nanococktails”

The construction of high‐performance nanotheranostic agent with Food and Drug Administration (FDA)‐approved materials for efficient treatment of breast cancer is still of great challenge. This work reports, for the first time, on the elaborate integration of two FDA‐approved materials together to construct a multifunctional core/shell‐structured “nanococktail” for cancer theranostics. The biocompatible Prussian blue nanoparticles with high photothermal‐conversion performance are coated by poly(lactic‐co‐glycolic acid) followed by further surface targeting engineering (folic acid conjugation). The anticancer drug paclitaxel is concurrently encapsulated into the nanocarrier with high efficiency and capacity. Especially, these “nanococktails” act as the desirable contrast agents for photoacoustic/magnetic resonance imaging dual‐mode diagnostic imaging, providing the potential for guidance and monitoring during the therapeutic process, which has been systematically demonstrated both in vitro and in vivo. Importantly, these “nanococktails” have demonstrated their high performance in synergistic in vivo photothermal therapy and chemotherapy against breast cancer tumor xenograft. This work not only provides a high‐performance theranostic “nanococktail” platform for efficient theranostic treatment of cancer but also paves a new way for the integration of various functional moieties together for realizing the specific diagnostic imaging‐guided and synergistic cancer therapy.     

Magnetic separation and SERS observation of analyte molecules on bifunctional silver/iron oxide composite nanostructures

We report the preparation of bifunctional silver–iron oxide composite nanostructures (Ag@Fe₂O₃) and demonstrate their magnetic separation with an analyte molecule from silver nanoparticles in a mixed solution. Magnetic and non‐magnetic plasmonic nanostructures and their separation are monitored by the surface‐enhanced Raman scattering (SERS) spectra of two different analytes attached to each kind of particles. In general, such separation experiments can provide insight into basic phenomena of adsorption and exchange of adsorbed molecules which are of strong interest in SERS. The formation of stable Ag@Fe₂O₃ nanoparticle–molecule complexes suggests small magnetic SERS labels without additional protective layers for application in analytical assays. The magnetic plasmonic nanostructures have great promise for targeted imaging and sensing in biological structures by directing nanosensors to places of interest using magnetic fields. The option of magnetic separation and collection of plasmonic particles improves the analytical capabilities of SERS. Copyright © 2012 John Wiley & Sons, Ltd.     

Analysis of high gradient magnetic field effects on distribution of nanoparticles injected into pulsatile blood stream

Magnetic nanoparticles are widely used in a wide range of applications including data storage materials, pharmaceutical industries as magnetic separation tools, anti-cancer drug carriers and micro valve applications. The purpose of the current study is to investigate the effect of a non-uniform magnetic field on bio-fluid (blood) with magnetic nanoparticles. The effect of particles as well as mass fraction on flow field and volume concentration is investigated. The governing non-linear differential equations, concentration and Navier-stokes are coupled with the magnetic field. To solve these equations, a finite volume based code is developed and utilized. A real pulsatile velocity is utilized as inlet boundary condition. This velocity is extracted from an actual experimental data. Three percent nanoparticles volume concentration, as drug carrier, is steadily injected in an unsteady, pulsatile and non-Newtonian flow. A power law model is considered for the blood viscosity. The results show that during the systole section of the heartbeat when the blood velocity increases, the magnetic nanoparticles near the magnetic source are washed away. This is due to the sudden increase of the hydrodynamic force, which overcomes the magnetic force. The probability of vein blockage increases when the blood velocity reduces during the diastole time. As nanoparticles velocity injection decreases (longer injection time) the wall shear stress (especially near the injection area) decreases and the retention time of the magnetic nanoparticles in the blood flow increases.     

Doxorubicin delivered to MCF-7 cancer cells by superparamagnetic iron oxide nanoparticles: effects on subcellular distribution and cytotoxicity

The clinical use of the anticancer drug doxorubicin (DOX) is limited by strong side effects and phenomena of cell resistance. Drug targeting by binding DOX to nanoparticles could overcome these limitations. We recently described a method to associate DOX to superparamagnetic iron oxide nanoparticles (SPION) in view of magnetic drug targeting (Munnier et al. in Int J Pharm 363:170–176, 2008). DOX is bound to the nanoparticle surface through a pre-formed DOX–Fe²⁺ complex. The DOX-loaded SPION present interesting properties in terms of drug loading and biological activity in vitro. The purpose of this study is to explore the possible mechanisms of the in vitro cytotoxicity of DOX-loaded SPION. The uptake of SPION was followed qualitatively by conventional optical microscopy after Prussian blue staining and quantitatively by iron determination by atomic absorption spectroscopy. The subcellular distribution of intrinsically fluorescent DOX was followed by confocal spectral imaging (CSI) and the subsequent cytotoxicity by the MTT method. We reveal modifications of DOX intracellular interactions for SPION-delivered drug and increased cytotoxicity. These results are discussed in terms of internalization route of the drug and of a potential role of iron oxide nanoparticles in the observed cytotoxicity.