Mesoporous silica beads embedded with semiconductor quantum dots and iron oxide nanocrystals: dual-function microcarriers for optical encoding and magnetic separation

Mesoporous beads are promising materials for embedding functional nanoparticles because of their nanometer-sized pores and large surface areas. Here we report the development of silica microbeads embedded with both semiconductor quantum dots (QD) and iron oxide (Fe3O4) nanocrystals as a new class of dual-function carriers for optical encoding and magnetic separation. The embedding (doping) process is carried out by either simultaneous or sequential addition of quantum dots and iron oxide (Fe3O4) nanocrystals in solution. The doping process is fast and quantitative, but the incorporated iron oxide strongly attenuates the signal intensity of QD fluorescence. We find that this attenuation is not due to conventional fluorescence quenching but is caused by the broad optical absorption spectrum of mixed-valence Fe3O4. For improved biocompatibility and reduced nonspecific binding, the encoded beads are further coated with amphiphilic polymers such as octylamine poly(acrylic acid). The results indicate that the polymer-coated beads are well suited for target capturing and enrichment, yielding magnetic separation efficiencies higher than 99%. By combining the multiplexing capability of QDs with the superparamagnetic properties of iron oxide nanocrystals, this class of encoded beads is expected to find broad applications in high-throughput and multiplexed biomolecular assays.     

Self-assembly of phospholipid-PEG coating on nanoparticles through dual solvent exchange

We coated nanoparticles including iron oxide nanoparticles and quantum dots with phospholipid-PEG using the newly developed dual solvent exchange method and demonstrated that, compared with the conventional film hydration method, the coating efficiency and quality of coated nanoparticles can be significantly improved. A better control of surface coating density and the amount of reactive groups on nanoparticle surface is achieved, allowing conjugation of different moieties with desirable surface concentrations, thus facilitating biomedical applications of nanoparticles.     

Fluorescent-magnetic hybrid nanostructures: preparation, properties, and applications in biology

Research on nanocomposite materials aims at developing nanoscale composites with innovative optical, chemical, and magnetic properties, all combined in one single nanostructure. In this scenario, nanostructures which show simultaneously fluorescent and magnetic features are of particular interest for pharmaceutical and biomedical applications. In this review, we will focus our attention on magnetic-fluorescent nanocomposite based on colloidal iron oxide nanocrystals combined with different classes of fluorophores which can be either organic dyes, such as fluoresceins, cyanines, porphyrins, or colloidal quantum dots. We will give an overview of the preparation methods of the magnetic-fluorescent nanocomposites that are now available and we will outline the most significant in vitro studies of such nanocomposites on living cells. Some examples of their applications in biology and medicine will also be discussed.     

Nanocrystal core high-density lipoproteins: a multimodality contrast agent platform

High density lipoprotein (HDL) is an important natural nanoparticle that may be modified for biomedical imaging purposes. Here we developed a novel technique to create unique multimodality HDL mimicking nanoparticles by incorporation of gold, iron oxide, or quantum dot nanocrystals for computed tomography, magnetic resonance, and fluorescence imaging, respectively. By including additional labels in the corona of the particles, they were made multifunctional. The characteristics of these nanoparticles, as well as their in vitro and in vivo behavior, revealed that they closely mimic native HDL.     

Simple method for coating Si (1 0 0) surfaces with ferritin monolayers—Iron oxide quantum dots

With the goal to develop iron oxide quantum dots we developed a simple method to spread horse spleen ferritin monolayers on a Si (1 0 0) surface. Application of atomic force microscopy and spectroscopic ellipsometry showed the existence of regions with dense ferritin monolayers. Application of transmission electron microscopy identified the core of the spread ferritin as FeO nanocrystals.     

Bi-layered polymer–magnetite core/shell particles: synthesis and characterization

Polymer magnetic core particles receive growing attention due to these materials owing magnetic properties which are widely used in different applications. The prepared composite particles are characterized with different properties namely: a magnetic core, a hydrophobic first shell, and finally an external second hydrophilic shell. The present study describes a method for the preparation of bi-layered polymer magnetic core particles (diameter range is 50–150 nm). This method comprises several steps including the precipitation of the magnetic iron oxide, coating the magnetite with oleic acid, attaching the first polymer shell by miniemulsion polymerization and finally introducing hydrophilic surface properties by condensation polymerization. The first step is the formation of magnetite nanoparticles within a co-precipitation process using oleic acid as the stabilizing agent for magnetite. The second step is the encapsulation of magnetite into polyvinylbenzyl chloride particles by miniemulsion polymerization to form a magnetic core with a hydrophobic polymer shell. The hydrophobic shell is desired to protect magnetite nanoparticles against chemical attack. The third step is the coating of magnetic core hydrophobic polymer shell composites with a hydrophilic layer of polyethylene glycol by condensation polymerization. Regarding the miniemulsion polymerization the influence of the amount of water, the mixing intensity and the surfactant concentration were studied with respect to the formation of particles which can be further used in chemical engineering applications. The resulting magnetic polymer nanoparticles were characterized by particle size measurement, chemical stability, iron content, TEM, SEM, and IR.     

Surface Engineering of Core/Shell Iron/Iron Oxide Nanoparticles from Microemulsions for Hyperthermia

This paper describes the synthesis and surface engineering of core/shell-type iron/iron oxide nanoparticles for magnetic hyperthermia cancer therapy. Iron/iron oxide nanoparticles were synthesized from microemulsions of NaBH(4) and FeCl(3), followed by surface modification in which a thin hydrophobic hexamethyldisilazane layer - used to protect the iron core - replaced the CTAB coating on the particles. Phosphatidylcholine was then assembled on the nanoparticle surface. The resulting nanocomposite particles have a biocompatible surface and show good stability in both air and aqueous solution. Compared to iron oxide nanoparticles, the nanocomposites show much better heating in an alternating magnetic field. They are good candidates for both hyperthermia and magnetic resonance imaging applications.     

Single Chain Epidermal Growth Factor Receptor Antibody Conjugated Nanoparticles for in vivo Tumor Targeting and Imaging

Epidermal growth factor receptor (EGFR) targeted nanoparticle are developed by conjugating a single‐chain anti‐EGFR antibody (ScFvEGFR) to surface functionalized quantum dots (QDs) or magnetic iron oxide (IO) nanoparticles. The results show that ScFvEGFR can be successfully conjugated to the nanoparticles, resulting in compact ScFvEGFR nanoparticles that specifically bind to and are internalized by EGFR‐expressing cancer cells, thereby producing a fluorescent signal or magnetic resonance imaging (MRI) contrast. In vivo tumor targeting and uptake of the nanoparticles in human cancer cells is demonstrated after systemic delivery of ScFvEGFR‐QDs or ScFvEGFR‐IO nanoparticles into an orthotopic pancreatic cancer model. Therefore, ScFvEGFR nanoparticles have potential to be used as a molecular‐targeted in vivo tumor imaging agent. Efficient internalization of ScFvEGFR nanoparticles into tumor cells after systemic delivery suggests that the EGFR‐targeted nanoparticles can also be used for the targeted delivery of therapeutic agents.     

Gelatin stabilized iron oxide nanoparticles as a three dimensional template for the hydroxyapatite crystal nucleation and growth

Inspired by the structural similarity of gelatin (and collagen) linked to a mineral phase based on Ca-phosphates compounds with natural bone and increasing application of magnetic iron oxides in hyperthermia, gelatin coated iron oxide (GIO) was synthesized and hydroxyapatite (HAp) crystal nucleation and growth in the nanoparticles was explored. A series of GIO/HAp nanocomposites with various amount of GIO were synthesized by co-precipitation technique using calcium hydroxide and phosphoric acid as precursor. Various physico-chemical analysis showed that the HAp crystal nucleation and growth occurred at acidic group of gelatin, while magnetic iron oxide nanoparticles (< 8nm) were bound to the amide groups of the gelatin chain. Moreover, the growth of HAp nanocrystals in aq. GIO solution was highly influenced by the GIO contents in the solution. The mineralized composite with magnetic properties could have great scope in biomedical field as a thermoseed to kill the cancerous cell in bone side by side for the bone reinforcement.     

A Review on Iron Oxide Nanoparticles and Their Biomedical Applications

The iron oxide nanoparticles have a great attraction in biomedical applications due to their non-toxic role in the biological systems. The iron oxide nanoparticles have both magnetic behaviour and semiconductor property which lead to multifunctional biomedical applications. The iron oxide nanoparticles used in biomedical fields such as antibacterial, antifungal and anticancer were reviewed. The uses of hematite (α-Fe₂O₃), maghemite (γ-Fe₂O₃) and magnetite (Fe₃O₄) nanoparticles, for an inhibition time in biological activities, are listed in this work. Also, this review explains the use of iron oxide nanoparticles in the biomedical fields with particular attention to the application of hematite and superparamagnetic iron oxide nanoparticles. In this review, analysis reveals that the role of iron oxide in biological activity is good due to its biocompatibility, biodegradability, ease of synthesis and different magnetic behaviours. The change of properties of iron oxide nanoparticles such as particle size, morphology, surface, agglomeration and electronic properties has specific impact in biomedical application. The review mainly focused in and discussed about antibacterial, anticancer, bone marrow and cell labelling activities. From this review work, the iron oxide nanoparticle may be specialised in particular bacterial and cancer treatments. Also discussed are the iron oxide nanoparticle-specific biomedical applications like human placenta, insulin and retinal locus treatments.     

核壳结构CdS/ZnS荧光量子点的制备与荧光性能研究

以氧化镉为镉源、硫单质为硫源、油酸为配体、在十八烯体系中合成单分散的CdS纳米颗粒,研究了配体浓度对纳米微粒的生长动力学、颗粒尺寸分布的影响.采用乙基黄原酸锌作为Zn、S源的反应前体,采用逐滴滴加的方法制备了具有核壳结构的CdS/ZnS量子点,吸收光谱和荧光光谱表明CdS/ZnS纳米粒子比单一的CdS纳米粒子具有更优异的发光特性.透射电子显微镜、X射线粉末衍射、X射线光电子能谱、选区电子衍射证明ZnS在CdS表面进行了有效包覆.所制备核壳结构纳米粒子具有较好的尺寸分布,荧光发射峰半高峰宽为18～20nm,荧光量子产率达40%.     

Detection of bioconjugated quantum dots passivated with different ligands for bio-applications

Bioconjugation of quantum dots has resulted in a significant increase in resolution of biological fluorescent labeling. This intrinsic property of quantum dots can be utilized for sensitive detection of target analytes with high sensitivity; including pathogenic bacteria and cancer monitoring. The quantum dots and quantum dot doped silica nanoparticles exhibit prominent emission peaks when excited at 400 nm but on conjugation to model rabbit antigoat antibodies exhibit diminished intensity of emission peak at 600 nm. It shows that photoluminescence intensity of conjugated quantum dots and quantum dot doped silica nanoparticles could permit the detection of bioconjugation. Samples of conjugated and unconjugated quantum dots and quantum dot doped silica nanoparticles were subjected to enzyme linked immunosorbent assay for further confirmation of bioconjugation. In the present study ligand exchange, bioconjugation, fluorescence detection of bioconjugated quantum dots and quantum dot doped silica nanoparticles and further confirmation of bioconjugation by enzyme linked immunosorbent assay has been described.     

Encapsulation of magnetic nanoparticles in a pH-sensitive poly(4-vinyl pyridine) polymer: a step forward to a multi-responsive system

A multiresponsive system that consists on pH-responsive polymer microspheres with encapsulated iron oxide magnetic nanoparticles that rendered the core magnetic to enable externally controlled actuation under magnetic induction has been developed. The inorganic nanoparticles were first prepared and, then, further encapsulated in a pH-sensitive poly(4-vinylpyridine). These spheres have been obtained by a modification of the simple, rapid and high-reproducible nanoprecipitation method. Magnetic measurements showed that the iron oxide nanoparticles are superparamagnetic and, therefore, able to undergo a local increase of the temperature when an oscillating magnetic field is applied. Magnetically triggered heating and pH sensitivity can be useful for biomedical applications.     

Synthesis of core-shell nanoclusters with high magnetic moment for biomedical applications

Biocompatible magnetic nanoparticles have been found to be promising in several biomedical applications for tagging, imaging, sensing, and separation in recent years. Most magnetic particles or beads currently used in biomedical applications are based on ferromagnetic iron oxides with very low specific magnetic moments of about 20-30 emu/g. Here, we report a new approach to synthesize monodispersive core-shell nanostructured clusters with high specific magnetic moments above 200 emu/g. The Fe nanoclusters, ranging in size from 2 to 100 nm, are produced from a newly developed cluster source and go to a deposition chamber, where a chemical reaction starts, and the nanoclusters are coated with Fe oxides. High-resolution transmission electron microscopy images show the coatings are very uniform. The core-shell nanoclusters are superparamagnetic at room temperature for sizes less than 12 nm, and have the coercivity of about 1.5 kOe at low temperature (5 K).     

Direct Observation of sp-d exchange interactions in colloidal Mn2+- and Co2+-doped CdSe quantum dots

The defining attribute of a diluted magnetic semiconductor (DMS) is the existence of dopant-carrier magnetic exchange interactions. In this letter, we report the first direct observation of such exchange interactions in colloidal doped CdSe nanocrystals. Doped CdSe quantum dots were synthesized by thermal decomposition of (Me4N)2[Cd4(SePh)10] in the presence of TMCl2 (TM2+ = Mn2+ or Co2+) in hexadecylamine and were characterized by several analytical and spectroscopic techniques. Using magnetic circular dichroism spectroscopy, successful doping and the existence of giant excitonic Zeeman splittings in both Mn2+- and Co2+-doped wurtzite CdSe quantum dots are demonstrated unambiguously.     

Metal oxide/polyaniline nanocomposites: Cluster size and composition dependent structural and magnetic properties

Nanocomposites of iron oxide with conducting polymer in the form of powders of varying compositions have been studied to understand the effects of particle size, cluster size and magnetic inter-particle interactions. The sizes of the nanoparticles were estimated to be ∼ 10–20 nm from the X-ray diffraction (XRD) and the transmission electron micrographs (TEM). XRD shows a single crystalline phase for the γ-Fe₂O₃. The presence of conducting polymer was confirmed through Fourier transform infrared (FTIR) spectroscopy. The amount of polymer present in the composite, the transition temperature of iron oxide and the thermal stability of polymer was determined through thermogravimetric and differential thermal analysis (TGA-DTA). The room temperature magnetic hysteresis measurements show reduction in saturation magnetization with increasing polymer concentrations. A low value of coercivity was observed for low polymer composites. On increasing the polymer concentration, the coercivity and remanence become negligible indicating a superparamagnetic phase at room temperature. Beyond a certain composition, the system shows paramagnetic behaviour which is also confirmed through zero field cooled-field cooled (ZFC-FC) measurements. We also report preliminary results on the magnetic properties of self standing sheets prepared using γ-Fe₂O₃ and NiFe₂O₄ nanoparticles and conducting polymers.     

Fabrication of surface magnetic nanoclusters using low energy ion implantation and electron beam annealing

Magnetic nanoclusters have novel applications as magnetic sensors, spintronic and biomedical devices, as well as applications in more traditional materials such as high-density magnetic storage media and high performance permanent magnets. We describe a new synthesis protocol which combines the advantages of ion implantation and electron beam annealing (EBA) to produce surface iron nanoclusters. We compare the structure, composition and magnetic properties of iron nanoclusters fabricated by low dose 15 keV Fe implantation into SiO(2) followed by 1000?°C EBA or furnace annealing. Atomic force microscopy (AFM) and high resolution transmission electron microscopy (HRTEM) images together with superconducting quantum interference device (SQUID) magnetometry measurements show that only EBA leads to the rapid formation of surface crystalline Fe spherical nanoclusters, showing magnetic moments per Fe atom comparable to that of bulk bcc Fe and superparamagnetic properties. We propose a fabrication mechanism which includes e-beam enhanced desorption of SiO(2). This method has potential for fabricating nanoscale magnetic sensors integrated in microelectronic devices.     

Enhanced pulsed magneto-motive ultrasound imaging using superparamagnetic nanoclusters

Recently, pulsed magneto-motive ultrasound (pMMUS) imaging augmented with ultra-small magnetic nanoparticles has been introduced as a tool capable of imaging events at molecular and cellular levels. The sensitivity of a pMMUS system depends on several parameters, including the size, geometry and magnetic properties of the nanoparticles. Under the same magnetic field, larger magnetic nanostructures experience a stronger magnetic force and produce larger displacement, thus improving the sensitivity and signal-to-noise ratio (SNR) of pMMUS imaging. Unfortunately, large magnetic iron-oxide nanoparticles are typically ferromagnetic and thus are very difficult to stabilize against colloidal aggregation. In the current study we demonstrate improvement of pMMUS image quality by using large size superparamagnetic nanoclusters characterized by strong magnetization per particle. Water-soluble magnetic nanoclusters of two sizes (15 and 55 nm average size) were synthesized from 3 nm iron precursors in the presence of citrate capping ligand. The size distribution of synthesized nanoclusters and individual nanoparticles was characterized using dynamic light scattering (DLS) analysis and transmission electron microscopy (TEM). Tissue mimicking phantoms containing single nanoparticles and two sizes of nanoclusters were imaged using a custom-built pMMUS imaging system. While the magnetic properties of citrate-coated nanoclusters are identical to those of superparamagnetic nanoparticles, the magneto-motive signal detected from nanoclusters is larger, i.e. the same magnetic field produced larger magnetically induced displacement. Therefore, our study demonstrates that clusters of superparamagnetic nanoparticles result in pMMUS images with higher contrast and SNR.     

Compact zwitterion-coated iron oxide nanoparticles for biological applications

The potential of superparamagnetic iron oxide nanoparticles (SPIONs) in various biomedical applications, including magnetic resonance imaging (MRI), sensing, and drug delivery, requires that their surface be derivatized to be hydrophilic and biocompatible. We report here the design and synthesis of a compact and water-soluble zwitterionic dopamine sulfonate (ZDS) ligand with strong binding affinity to SPIONs. After ligand exchange, the ZDS-coated SPIONs exhibit small hydrodynamic diameters, and stability with respect to time, pH, and salinity. Furthermore, small ZDS coated SPIONs were found to have a reduced nonspecific affinity (compared to negatively charged SPIONs) toward serum proteins; streptavidin/dye functionalized SPIONs were bioactive and thus specifically targeted biotin receptors.     

Synthesis of silica-coated aqueous ferrofluids through ligand exchange with a new organosilica precursor

A new method for the production of aqueous dispersions of superparamagnetic iron oxide nanoparticles with applications in biomedicine is reported. The method is based on the use of a triethoxisilyl dodecanoic acid ligand that has been specially synthesized for this purpose. The nanoparticles were grown in organic medium using oleic acid as surfactant. Subsequently, oleic acid was exchanged for the alkoxysilane ligand, then hydrolysis was performed in a hydrocarbon solvent, and the nanoparticles were transferred into water. The organic and aqueous ferrofluids have been characterized and their magnetic properties have been determined. The resulting maghemite/silica nanoparticles were single core, and stable in aqueous suspension.