Surface modulation of magnetic nanocrystals in the development of highly efficient magnetic resonance probes for intracellular labeling

High-quality biocompatible magnetic iron oxide (Fe3O4) nanocrystals were developed through a ligand exchange process of hydrophobically capped nanocrystals with hydrophilic molecules. By simple modulation of the nanocrystal surface ligand charge properties, we have been able to prepare magnetic nanocrystals with excellent intracellular labeling capabilities that efficiently label a variety of cell types without the need for additional transport facilitating agents. The excellent intracellular labeling capability of the newly developed cationic WSIO has further led to successful MRI monitoring of the migration of neural stem cells in rat spinal cord. The magnetic nanocrystals developed here have great potential in applications for labeling of various cell types and also the monitoring of cell-based medical treatments and cancer metastasis.     

Nanoscale size effect of magnetic nanocrystals and their utilization for cancer diagnosis via magnetic resonance imaging

Since the use of magnetic nanocrystals as probes for biomedical system is attractive, it is important to develop optimal synthetic protocols for high-quality magnetic nanocrystals and to have the systematic understanding of their nanoscale properties. Here we present the development of a synthetically controlled magnetic nanocrystal model system that correlates the nanoscale tunabilities in terms of size, magnetism, and induced nuclear spin relaxation processes. This system further led to the development of high-performance nanocrystal-antibody probe systems for the diagnosis of breast cancer cells via magnetic resonance imaging.     

Enhancement of magnetic resonance contrast effect using ionic magnetic clusters

Precise diagnosis by magnetic resonance imaging (MRI) requires sensitive magnetic resonance probes to detect low concentrations of magnetic substances. Ionic magnetic clusters (IMCs) as versatile magnetic probes were successfully synthesized for enhancing the magnetic resonance (MR) contrast effect as well as ensuring high water solubility. IMCs with various sizes were prepared by assembly of MNCs using cationic cetyltrimethylammonium bromide (CTAB) and anionic sodium dodecyl sulfate (SDS). To synthesize IMCs in the aqueous phase, magnetic nanocrystals in an organic solvent were assembled with CTAB and SDS using the nanoemulsion method, to fabricate cationic magnetic clusters (CMCs) and anionic magnetic clusters (AMCs), respectively. IMCs demonstrated ultrasensitivity by MR imaging and sufficient magnetic mobility under an external magnetic field.     

Study of nucleation and growth in the organometallic synthesis of magnetic alloy nanocrystals: the role of nucleation rate in size control of CoPt3 nanocrystals

High quality CoPt(3) nanocrystals were synthesized via simultaneous reduction of platinum acetylacetonate and thermodecomposition of cobalt carbonyl in the presence of 1-adamantanecarboxylic acid and hexadecylamine as stabilizing agents. The high flexibility and reproducibility of the synthesis allows us to consider CoPt(3) nanocrystals as a model system for the hot organometallic synthesis of metal nanoparticles. Different experimental conditions (reaction temperature, concentration of stabilizing agents, ratio between cobalt and platinum precursors, etc.) have been investigated to reveal the processes governing the formation of the metal alloy nanocrystals. It was found that CoPt(3) nanocrystals nucleate and grow up to their final size at an early stage of the synthesis with no Ostwald ripening observed upon further heating. In this case, the nanocrystal size can be controlled only via proper balance between the rates for nucleation and for growth from the molecular precursors. Thus, the size of CoPt(3) nanocrystals can be precisely tuned from approximately 3 nm up to approximately 18 nm in a predictable and reproducible way. The mechanism of homogeneous nucleation, evolution of the nanocrystal ensemble in the absence of Ostwald ripening, nanocrystal faceting, and size-dependent magnetic properties are investigated and discussed on the example of CoPt(3) magnetic alloy nanocrystals. The developed approach was found to be applicable to other systems, e.g., FePt and CoPd(2) magnetic alloy nanocrystals.     

One-pot synthesis of highly monodispersed ferrite nanocrystals: surface characterization and magnetic properties

In the present study, a facile one-pot synthetic route, utilizing a strong polar organic solvent, N-methyl 2-pyrrolidone (NMP), is demonstrated to obtain highly monodispersed ferrite nanocrystals. The equimolar mixture of oleic acid, C(17)H(33)COOH (R-COOH), and oleylamine, C(18)H(35)NH(2) (R'-NH(2)), was used to coat the magnetic nanocrystals. Structural and magnetic properties of the ferrite nanocrystals were studied by a multitechnique approach including X-ray diffraction (XRD), high resolution transmission electron microscopy (HRTEM), Fourier transform infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA), X-ray photoelectron spectroscopy (XPS), vibrating sample magnetometry (VSM), and M?ssbauer spectroscopy. FTIR spectral analysis indicates oleylamine helps in deprotonation of oleic acid, resulting in the formation of an acid-base complex, R-COOˉ:NH(3)(+)-R', which acts as binary capping agent. Structural and coordination differences of iron were studied by XPS and M?ssbauer spectral analysis. XPS analysis was carried out to examine the oxidation state of iron ions in iron oxide nanocrystals. The presence of a magnetically dead layer (～0.38 and ～0.67 nm) and a nonmagnetic organic coating (～2.3 and ～1.7 nm) may substantially reduce the saturation magnetization values for CoFe(2)O(4) and Fe(3)O(4) nanocrystals, respectively. The energy barrier distribution function of magnetic anisotropy was derived from the temperature dependent decay of magnetization. A very narrow energy barrier distribution elucidates that the ferrite nanocrystals obtained in this study are highly monodispersed.     

Seeded growth of asymmetric binary nanocrystals made of a semiconductor TiO2 rodlike section and a magnetic gamma-Fe2O3 spherical domain

Asymmetric binary nanocrystals (BNCs), comprising one c-axis elongated anatase TiO2 section and one gamma-Fe2O3 spherical domain attached together, are synthesized by heterogeneous nucleation of iron oxide onto the longitudinal facets of TiO2 nanorods in a ternary surfactant mixture. The topologically controlled composition of the BNCs is ascertained by a combination of powder X-ray diffraction, Raman and M?ssbauer spectroscopy, high-angle annular dark-field imaging, and high-resolution transmission electron microscopy lattice fringe mapping, while their size-dependent magnetic behavior is demonstrated by ac susceptibility measurements. The heteroepitaxial growth proceeds through a mechanism never observed before for colloidal nanoheterostructures: the two domains share a restricted and locally curved junction region, which accommodates efficiently the interfacial strain and retards the formation of misfit dislocations. It is believed that these BNCs, which combine the properties of two technologically relevant oxide materials, can pave the way to reinforced applications in several fields of nanoscience, such as in photocatalysis, in malignant cell treatments, and in nanocrystal assembly.     

磁性氧化铁纳米颗粒——通向肿瘤磁共振分子影像的重要基石

本文根据近年来国内外发表的相关研究成果,总结了磁性氧化铁纳米晶体制备方面的研究进展,并以磁性氧化铁纳米颗粒在肿瘤磁共振分子影像领域中的应用为背景,阐述了肿瘤分子影像领域的未来发展趋势.     

A Comparative Study of Receptor-Targeted Magnetosome and HSA-Coated Iron Oxide Nanoparticles as MRI Contrast-Enhancing Agent in Animal Cancer Model

Magnetosomes are specialized organelles arranged in intracellular chains in magnetotactic bacteria. The superparamagnetic property of these magnetite crystals provides potential applications as contrast-enhancing agents for magnetic resonance imaging. In this study, we compared two different nanoparticles that are bacterial magnetosome and HSA-coated iron oxide nanoparticles for targeting breast cancer. Both magnetosomes and HSA-coated iron oxide nanoparticles were chemically conjugated to fluorescent-labeled anti-EGFR antibodies. Antibody-conjugated nanoparticles were able to bind the MDA-MB-231 cell line, as assessed by flow cytometry. To compare the cytotoxic effect of nanoparticles, MTT assay was used, and according to the results, HSA-coated iron oxide nanoparticles were less cytotoxic to breast cancer cells than magnetosomes. Magnetosomes were bound with higher rate to breast cancer cells than HSA-coated iron oxide nanoparticles. While 250 μg/ml of magnetosomes was bound 92 ± 0.2%, 250 μg/ml of HSA-coated iron oxide nanoparticles was bound with a rate of 65 ± 5%. In vivo efficiencies of these nanoparticles on breast cancer generated in nude mice were assessed by MRI imaging. Anti-EGFR-modified nanoparticles provide higher resolution images than unmodified nanoparticles. Also, magnetosome with anti-EGFR produced darker image of the tumor tissue in T2-weighted MRI than HSA-coated iron oxide nanoparticles with anti-EGFR. In vivo MR imaging in a mouse breast cancer model shows effective intratumoral distribution of both nanoparticles in the tumor tissue. However, magnetosome demonstrated higher distribution than HSA-coated iron oxide nanoparticles according to fluorescence microscopy evaluation. According to the results of in vitro and in vivo study results, magnetosomes are promising for targeting and therapy applications of the breast cancer cells.     

Bioactivation and cell targeting of semiconductor CdSe/ZnS nanocrystals with phytochelatin-related peptides

Synthetic phytochelatin-related peptides are used as an organic coat on the surface of colloidal CdSe/ZnS semiconductor nanocrystals synthesized from hydrophobic coordinating trioctyl phosphine oxide (TOPO) solvents. The peptides are designed to bind to the nanocrystals via a C-terminal adhesive domain. This adhesive domain, composed of multiple repeats of cysteines pairs flanked by hydrophobic 3-cyclohexylalanines, is followed by a flexible hydrophilic linker domain to which various bio-affinity tags can be attached. This surface coating chemistry results in small, buffer soluble, monodisperse peptide-coated nanoparticles with high colloidal stability and ensemble photophysical properties similar to those of TOPO-coated nanocrystals. Various peptide coatings are used to modulate the nanocrystal surface properties and to bioactivate the nanoparticles. CdSe/ZnS nanocrystals coated with biotinylated peptides efficiently bind to streptavidin and are specifically targeted to GPI-anchored avidin-CD14 chimeric proteins expressed on the membranes of live HeLa cells. This peptide coating surface chemistry provides a novel approach for the production of biocompatible photoluminescent nanocrystal probes.     

Multifunctional particles: Magnetic nanocrystals and gold nanorods coated with fluorescent dye-doped silica shells

Multifunctional colloidal core-shell nanoparticles of magnetic nanocrystals (of iron oxide or FePt) or gold nanorods encapsulated in silica shells doped with the fluorescent dye, Tris(2,2′-bipyridyl)dichlororuthenium(II) hexahydrate (Rubpy) were synthesized. The as-prepared magnetic nanocrystals are initially hydrophobic and were coated with silica using a microemulsion approach, while the as-prepared gold nanorods are hydrophilic and were coated with silica using a Stöber type of process. Each approach yielded monodisperse nanoparticles with uniform fluorescent dye-doped silica shells. These colloidal heterostructures have the potential to be used as dual-purpose tags—exhibiting a fluorescent signal that could be combined with either dark-field optical contrast (in the case of the gold nanorods), or enhanced contrast in magnetic resonance images (in the case of magnetic nanocrystal cores). The optical and magnetic properties of the fluorescent silica-coated gold nanorods and magnetic nanocrystals are reported.     

Synthesis of magnetic nanoparticles and their application to bioassays

Magnetic nanoparticles have been attracting much interest as a labeling material in the fields of advanced biological and medical applications such as drug delivery, magnetic resonance imaging, and array-based assaying. In this review, synthesis of iron oxide magnetic nanoparticles via a reverse micelle system and modification of their surface by an organosilane agent are discussed. Furthermore, as a practical biological assay system, the magnetic detection of biomolecular interactions is demonstrated by using the combination of a patterned substrate modified with a self-assembled monolayer and the magnetic nanoparticles.     

Designed synthesis of uniformly sized iron oxide nanoparticles for efficient magnetic resonance imaging contrast agents

Various magnetic nanoparticles have been extensively investigated as novel magnetic resonance imaging (MRI) contrast agents owing to their unique characteristics, including efficient contrast effects, biocompatibility, and versatile surface functionalization capability. Nanoparticles with high relaxivity are very desirable because they would increase the accuracy of MRI. Recent progress in nanotechnology enables fine control of the size, crystal structure, and surface properties of iron oxide nanoparticles. In this tutorial review, we discuss how MRI contrast effects can be improved by controlling the size, composition, doping, assembly, and surface properties of iron-oxide-based nanoparticles.     

Colloidal transition-metal-doped ZnO quantum dots

Methods for introducing new magnetic, optical, electronic, photophysical, or photochemical properties to semiconductor nanocrystals are attracting intense applications-oriented interest. In this communication, we report the preparation and electronic absorption spectroscopy of colloidal ZnO DMS-QDs. Our synthetic procedure involves modification of literature methods known to yield highly crystalline and relatively monodisperse nanocrystals of pure ZnO to allow introduction of transition-metal dopants. We use ligand-field electronic absorption spectroscopy as a dopant-specific optical probe to monitor dopant incorporation during nanocrystal growth and to verify internal substitutional doping in Co2+:ZnO and Ni2+:ZnO DMS-QDs. To the best of our knowledge, these are the first free-standing oxide DMS-QDs reported. The synthesis of colloidal oxide DMS-QDs introduces a new category of magnetic semiconductor materials available for detailed physical study and application in nanotechnology.     

Design of water-based ferrofluids as contrast agents for magnetic resonance imaging

We report the synthesis, characterization and relaxometric study of ferrofluids based on iron oxide, with potential for use as magnetic resonance imaging (MRI) contrast agents (CAs). The effect of different cost-effective, water-based surface modification approaches which can be easily scaled-up for the large scale synthesis of the ferrofluids has been investigated. Surface modification was achieved by silanization, and/or coating with non-toxic commercial dispersants (a lauric polysorbate and a block copolymer with pigment affinic groups, namely Tween 20 and Disperbyk 190) which were added after or during iron oxide nanoparticle synthesis. It was observed that all the materials synthesized functioned as negative contrast agents at physiological temperature and at frequencies covered by clinical imagers. The relaxometric properties of the magnetic nanoparticles were significantly improved after surface coating with stabilizers compared to the original iron oxide nanoparticles, with particular reference to the silica-coated magnetic nanoparticles. The results indicate that the optimization of the preparation of colloidal magnetic ferrofluids by surface modification is effective in the design of novel contrast agents for MRI by enabling better or more effective interaction between the coated iron oxide nanoparticles and protons present in their aqueous environment.     

Magnetite nanocrystal clusters with ultra-high sensitivity in magnetic resonance imaging

Magnetic iron oxide particles are widely used as contrast agents to improve the sensitivity of magnetic resonance imaging (MRI). Their efficiency in MRI is usually quantified by transverse relaxivity (r(2)) in solution. Herein, we synthesized a series of magnetite nanocrystal clusters (MNCs) with ultra-high transverse relaxivity by a polyol process and studied the relationship between r(2) and size of the MNCs. The sizes of MNCs can be tuned over a wide range from 13 to 179 nm. The r(2) of MNC suspensions as a function of the size of the cluster was analyzed and compared with a theoretical model. We found that MNCs of 64 nm had an r(2) value of 650 mM(-1) s(-1), which was more than three times that of the commercial contrast agent and was among the highest reported for iron oxide materials. Compared with the theoretical model, the r(2) value of the MNC suspension is approximately 0.93 of the theoretical prediction. Imaging of the MNC suspensions was performed in a clinical 1.5 T MRI instrument and a comparison was made between MNCs and commercial contrast agents. MRI indicated that the decrease of signal intensity induced by MNCs was in proportion to the r(2) value, which was in accordance with theoretical predictions. These results demonstrate that MNCs with ultra-high transverse relaxivity and tunable size are promising candidates for molecular imaging and clinical diagnosis in MRI.     

氧化铁磁性纳米粒子的制备、表面修饰及在分离和分析中的应用

氧化铁磁性纳米粒子通过表面化学修饰得到无机、有机或聚合物壳包覆在其表面。其中的壳结构既具有生物适应性,又具有可键合生物分子如细胞、蛋白质、酶、抗体和核酸的活性基团,而核具有磁性特性。本文总结了氧化铁磁性纳米粒子的制备方法,介绍了其表面化学修饰及在分离和分析应用的最新进展。     

Shape control and associated magnetic properties of spinel cobalt ferrite nanocrystals

By combining nonhydrolytic reaction with seed-mediated growth, high-quality and monodisperse spinel cobalt ferrite, CoFe(2)O(4), nanocrystals can be synthesized with a highly controllable shape of nearly spherical or almost perfectly cubic. The shape of the nanocrystals can also be reversibly interchanged between spherical and cubic morphology through controlling nanocrystal growth rate. Furthermore, the magnetic studies show that the blocking temperature, saturation, and remanent magnetization of nanocrystals are solely determined by the size regardless the spherical or cubic shape. However, the shape of the nanocrystals is a dominating factor for the coercivity of nanocrystals due to the effect of surface anisotropy. Such magnetic nanocrystals with distinct shapes possess tremendous potentials in fundamental understanding of magnetism and in technological applications of magnetic nanocrystals for high-density information storage.     

Ultrasensitive detection and molecular imaging with magnetic nanoparticles

Recent advances in nanotechnology have produced a variety of nanoparticles ranging from semiconductor quantum dots (QDs), magnetic nanoparticles (MNPs), metallic nanoparticles, to polymeric nanoparticles. Their unique electronic, magnetic, and optical properties have enabled a broad spectrum of biomedical applications such as ultrasensitive detection, medical imaging, and specific therapeutics. MNPs made from iron oxide, in particular, have attracted extensive interest and have already been used in clinical studies owing to their capability of deep-tissue imaging, non-immunogenesis, and low toxicity. In this Research Highlight article, we attempt to highlight the recent breakthroughs in MNP synthesis based on a non-hydrolytic approach, nanoparticle (NP) surface engineering, their unique structural and magnetic properties, and current applications in ultrasensitive detection and imaging with a special focus on innovative bioassays. We will also discuss our perspectives on future research directions.     

Constraints in post-synthesis ligand exchange for hybrid organic (MEH-PPV)–inorganic (CdSe) nanocomposites

For an optimum charge/energy transfer performance of hybrid organic–inorganic colloidal nanocrystals for applications such as photonic devices and solar cells, the determining factors are the distance between the nanocrystal and polymer which greatly depends upon nanocrystal size/nanocrystal ligands. Short chain ligands are preferred to ensure a close contact between the donor and acceptor as a result of the tunnelling probability of the charges and the insulating nature of long alkyl chain molecules. Short distances increase the probability for tunnelling to occur as compared to long distances induced by long alkyl chains of bulky ligands which inhibit tunnelling altogether. The ligands on the as-synthesized nanocrystals can be exchanged for various other ligands to achieve desirable charge/energy transfer properties depending on the bond strength of the ligand on the nanocrystal compared to the replacement ligand. In this work, the constraints involved in post-synthesis ligand exchange process have been evaluated, and these factors have been tuned via wet chemistry to tailor the hybrid material properties via appropriate selection of the nanocrystal capping ligands. It has been found that both oleic acid and oleylamine (OLA)-capped cadmium selenide (CdSe) quantum dots (QDs) as compared with trioctylphosphine oxide (TOPO)-passivated CdSe QDs are of high quality, and they provide better steric stability against coagulation, homogeneity, and photostability to their respective polymer:CdSe nanocomposites. CdSe QDs particularly with OLA capping have relatively smaller surface energies, and thus, lesser quenching capabilities show dominance of photoinduced Forster energy transfer between donors (polymer) and acceptors (CdSe nanocrystals) as compared to charge transfer mechanism as observed in polymer:CdSe (TOPO) composites. It is conjectured that size quantization effects, stereochemical compatibility of ligands (TOPO, oleic acid, and oleyl amine), and polymer MEH-PPV stability greatly influence the photophysics and photochemistry of hybrid polymer–semiconductor nanocomposites.     

Chemical design of nanoparticle probes for high-performance magnetic resonance imaging

Synthetic magnetic nanoparticles (MNPs) are emerging as versatile probes in biomedical applications, especially in the area of magnetic resonance imaging (MRI). Their size, which is comparable to biological functional units, and their unique magnetic properties allow their utilization as molecular imaging probes. Herein, we present an overview of recent breakthroughs in the development of new synthetic MNP probes with which the sensitive and target-specific observation of biological events at the molecular and cellular levels is possible.