Highly Loaded Semipermeable Nanocapsules for Magnetic Resonance Imaging

Magnetic resonance imaging has become an essential tool in medicine for the investigation of physiological processes. The key issues related to contrast agents, i.e., substances that are injected in the body for imaging, are the efficient enhancement of contrast, their low toxicity, and their defined biodistribution. Polyurea nanocapsules containing the gadolinium complex Gadobutrol as a contrast agent in high local concentration and high relaxivity up to 40 s⁻¹ mmol⁻¹ L are described. A high concentration of the contrast agent inside the nanocapsules can be ensured by increasing the crystallinity in the shell of the nanocapsules. Nanocapsules from aliphatic polyurea are found to display higher crystallinity and higher relaxivity at an initial Gadobutrol concentration of 0.1 m than aromatic polyurea nanocapsules. The nanocapsules and the contrast agent are clearly identified in cells. After injection, the nanocarriers containing the contrast agent are mostly found in the liver and in the spleen, which allow for a significant contrast enhancement in magnetic resonance imaging.     

Hybrid gadolinium oxide nanoparticles: multimodal contrast agents for in vivo imaging

Luminescent hybrid nanoparticles with a paramagnetic Gd2O3 core were applied as contrast agents for both in vivo fluorescence and magnetic resonance imaging. These hybrid particles were obtained by encapsulating Gd2O3 cores within a polysiloxane shell which carries organic fluorophores and carboxylated PEG covalently tethered to the inorganic network. Longitudinal proton relaxivities of these particles are higher than the positive contrast agents like Gd-DOTA which are commonly used for clinical magnetic resonance imaging. Moreover these particles can be followed up by fluorescence imaging. This study revealed that these particles suited for dual modality imaging freely circulate in the blood vessels without undesirable accumulation in lungs and liver.     

Paramagnetic gold nanostructures for dual modal bioimaging and phototherapy of cancer cells

Paramagnetic gold nanostructures were synthesized by combining the paramagnetism of gadolinium with the plasmonic properties of gold nanoparticles and used for dual modal (MRI and optical) imaging and phototherapy of breast cancer cells.     

A new sample substrate for imaging and correlating organic and trace metal composition in biological cells and tissues

Many disease processes involve alterations in the chemical makeup of tissue. Synchrotron-based infrared (IR) and X-ray fluorescence (XRF) microscopes are becoming increasingly popular tools for imaging the organic and trace metal compositions of biological materials, respectively, without the need for extrinsic labels or stains. Fourier transform infrared microspectroscopy (FTIRM) provides chemical information on the organic components of a material at a diffraction-limited spatial resolution of 2–10 μm in the mid-infrared region. The synchrotron X-ray fluorescence (SXRF) microprobe is a complementary technique used to probe trace element content in the same systems with a similar spatial resolution. However to be most beneficial, it is important to combine the results from both imaging techniques on a single sample, which requires precise overlap of the IR and X-ray images. In this work, we have developed a sample substrate containing a gold grid pattern on its surface, which can be imaged with both the IR and X-ray microscopes. The substrate consists of a low trace element glass slide that has a gold grid patterned on its surface, where the major and minor parts of the grid contain 25 and 12 nm gold, respectively. This grid pattern can be imaged with the IR microscope because the reflectivity of gold differs as a function of thickness. The pattern can also be imaged with the SXRF microprobe because the Au fluorescence intensity changes with gold thickness. The tissue sample is placed on top of the patterned substrate. The grid pattern’s IR reflectivity image and the gold SXRF image are used as fiducial markers for spatially overlapping the IR and SXRF images from the tissue. Results show that IR and X-ray images can be correlated precisely, with a spatial resolution of less than one pixel (i.e., 2–3 microns). The development of this new tool will be presented along with applications to paraffin-embedded metalloprotein crystals, Alzheimer’s disease, and hair composition.     

Spatially Resolved Quantification of Gadolinium(III)‐Based Magnetic Resonance Agents in Tissue by MALDI Imaging Mass Spectrometry after In Vivo MRI

Gadolinium(III)‐based contrast agents improve the sensitivity and specificity of magnetic resonance imaging (MRI), especially when targeted contrast agents are applied. Because of nonlinear correlation between the contrast agent concentration in tissue and the MRI signal obtained in vivo, quantification of certain biological or pathophysiological processes by MRI remains a challenge. Up to now, no technology has been able to provide a spatially resolved quantification of MRI agents directly within the tissue, which would allow a more precise verification of in vivo imaging results. MALDI imaging mass spectrometry for spatially resolved in situ quantification of gadolinium(III) agents, in correlation to in vivo MRI, were evaluated. Enhanced kinetics of Gadofluorine M were determined dynamically over time in a mouse model of myocardial infarction. MALDI imaging was able to corroborate the in vivo imaging MRI signals and enabled in situ quantification of the gadolinium probe with high spatial resolution.     

Preparation, characterization, and optical properties of gold, silver, and gold-silver alloy nanoshells having silica cores

This report describes the structural and optical properties of a series of spherical shell/core nanoparticles in which the shell is comprised of a thin layer of gold, silver, or gold-silver alloy, and the core is comprised of a monodispersed silica nanoparticle. The silica core particles were prepared using the St?ber method, functionalized with terminal amine groups, and then seeded with small gold nanoparticles (approximately 2 nm in diameter). The gold-seeded silica particles were coated with a layer of gold, silver, or gold-silver alloy via solution-phase reduction of an appropriate metal ion or mixture of metal ions. The size, morphology, and elemental composition of the composite nanoparticles were characterized by field emission scanning electron microscopy (FE-SEM), energy-dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), Fourier transform infrared (FT-IR) spectroscopy, thermal gravimetric analysis (TGA), dynamic light scattering (DLS), and transmission electron microscopy (TEM). The optical properties of the nanoparticles were analyzed by UV-vis spectroscopy, which showed strong absorptions ranging from 400 nm into the near-IR region, where the position of the plasmon band reflected not only the thickness of the metal shell, but also the nature of the metal comprising the shell. Importantly, the results demonstrate a new strategy for tuning the position of the plasmon resonance without having to vary the core diameter or the shell thickness.     

Multivalent interaction and selectivities in selectin binding of functionalized gold colloids decorated with carbohydrate mimetics

Colloidal gold particles with functionalized organic shells were applied as novel selectin binders. The ligand shell was terminated with different monocyclic carbohydrate mimetics as simplified analogs of the sLe(x) unit found in biological selectin ligands. The multivalent presentation of the sulfated selectin binding epitopes on the gold particles led to extremely high binding affinities towards L- and P-selectin and IC(50) values in the subnanomolar range. Depending on the ring size of the sulfated carbohydrate mimetic, its substitution pattern and its configuration, different selectivities for either L-selectin or P-selectin were obtained. These selectivities were not found for gold particles with simple acyclic sulfated alcohols, diols and triols in the ligand shell. In addition, the influence of the particle size and the thickness of the hydrophobic organic shell were systematically investigated.     

Solute-solvent halogen bonding during adsorption on silver nanostructures

Multimodal imaging technique is an alternative approach to improve sensitivity of early cancer diagnosis. In this study, highly fluorescent and strong X-ray absorption coefficient gold nanoclusters (Au NCs) are synthesized as dual-modality imaging contrast agents (CAs) for fluorescent and X-ray dual-modality imaging. The experimental results show that the as-prepared Au NCs are well constructed with ultrasmall sizes, reliable fluorescent emission, high computed tomography (CT) value and fine biocompatibility. In vivo imaging results indicate that the obtained Au NCs are capable of fluorescent and X-ray enhanced imaging.     

Antibiofouling polymer-coated gold nanoparticles as a contrast agent for in vivo X-ray computed tomography imaging

Current computed tomography (CT) contrast agents such as iodine-based compounds have several limitations, including short imaging times due to rapid renal clearance, renal toxicity, and vascular permeation. Here, we describe a new CT contrast agent based on gold nanoparticles (GNPs) that overcomes these limitations. Because gold has a higher atomic number and X-ray absorption coefficient than iodine, we expected that GNPs can be used as CT contrast agents. We prepared uniform GNPs ( approximately 30 nm in diameter) by general reduction of HAuCl4 by boiling with sodium citrate. The resulting GNPs were coated with polyethylene glycol (PEG) to impart antibiofouling properties, which extends their lifetime in the bloodstream. Measurement of the X-ray absorption coefficient in vitro revealed that the attenuation of PEG-coated GNPs is 5.7 times higher than that of the current iodine-based CT contrast agent, Ultravist. Furthermore, when injected intravenously into rats, the PEG-coated GNPs had a much longer blood circulation time (>4 h) than Ultravist (<10 min). Consequently, CT images of rats using PEG-coated GNPs showed a clear delineation of cardiac ventricles and great vessels. On the other hand, relatively high levels of GNPs accumulated in the spleen and liver, which contain phagocytic cells. Intravenous injection of PEG-coated GNPs into hepatoma-bearing rats resulted in a high contrast ( approximately 2-fold) between hepatoma and normal liver tissue on CT images. These results suggest that PEG-coated GNPs can be useful as a CT contrast agent for a blood pool and hepatoma imaging.     

Paclitaxel-functionalized gold nanoparticles

Here we describe the first example of 2 nm gold nanoparticles (Au NPs) covalently functionalized with a chemotherapeutic drug, paclitaxel. The synthetic strategy involves the attachment of a flexible hexaethylene glycol linker at the C-7 position of paclitaxel followed by coupling of the resulting linear analogue to phenol-terminated gold nanocrystals. The reaction proceeds under mild esterification conditions and yields the product with a high molecular weight, while exhibiting an extremely low polydispersity index (1.02, relative to linear polystyrene standards). TGA analysis of the hybrid nanoparticles reveals the content of the covalently attached organic shell as nearly 67% by weight, which corresponds to approximately 70 molecules of paclitaxel per 1 nanoparticle. The presence of a paclitaxel shell with a high grafting density renders the product soluble in organic solvents and allows for detailed (1)H NMR analysis and, therefore, definitive confirmation of its chemical structure. High-resolution TEM was employed for direct visualization of the inorganic core of hybrid nanoparticles, which were found to retain their average size, shape, and high crystallinity after multiple synthetic steps and purifications. The interparticle distance substantially increases after the attachment of paclitaxel as revealed by low-magnification TEM, suggesting the presence of a larger organic shell. The method described here demonstrates that organic molecules with exceedingly complex structures can be covalently attached to gold nanocrystals in a controlled manner and fully characterized by traditional analytical techniques. In addition, this approach gives a rare opportunity to prepare hybrid particles with a well-defined amount of drug and offers a new alternative for the design of nanosized drug-delivery systems.     

Gold‐loading magnetic core–shell organic/inorganic nanocomposites: facile preparation and multiple properties

Magnetic composite nanospheres (MCS) were first prepared via mini‐emulsion polymerization. Subsequently, the hybrid core–shell nanospheres were used as carriers to support gold nanoparticles. The as‐prepared gold‐loading magnetic composite nanospheres (Au‐MCS) had a hydrophobic core embed with γ‐Fe₃O₄ and a hydrophilic shell loaded by gold nanoparticles. Both the content of γ‐Fe₃O₄ and the size of gold nanoparticles could be controlled in our experiments, which resulted in fabricating various materials. On one hand, the Au‐MCS could be used as a T₂ contrast agent with a relaxivity coefficient of 362 mg^?1 ml S^?1 for magnetic resonance imaging. On the other hand, the Au‐MCS exhibited tunable optical‐absorption property over a wavelength range from 530 nm to 800 nm, which attributed to a secondary growth of gold nanoparticles. In addition, dynamic light scattering results of particle sizing and Zeta potential measurements revealed that Au‐MCS had a good stability in an aqueous solution, which would be helpful for further applications. Finally, it showed that the Au‐MCS were efficient catalysts for reductions of hydrophobic nitrobenzene and hydrophilic 4‐nitrophenol that could be reused by a magnetic separation process. Copyright © 2014 John Wiley & Sons, Ltd.     

聚苯胺包裹的金纳米粒子的合成和表征及初步应用

用苯胺作还原剂还原氯金酸合成了金纳米结构. TEM实验表明, 苯胺还原氯金酸能生成苯胺齐聚物或其聚合物包裹的金球形纳米粒子. XPS分析表明, 金纳米粒子包覆的聚合物层带正电荷. 该纳米粒子能用于电极表面纳米结构组装及氧化还原性的生物大分子的电化学研究, 实现了超氧化物歧化酶(SOD)在这种带正电荷的金纳米粒子表面的直接电子转移.     

Double hydrophilic block copolymer monolayer protected hybrid gold nanoparticles and their shell cross-linking

This paper describes the syntheses of core/shell gold nanoparticles stabilized with a monolayer of double hydrophilic block copolymer and their stimuli responsiveness before and after shell cross-linking. The hybrid nanoparticles consist of gold core, cross-linkable poly(2-(dimethylamino)ethyl methacrylate) (PDMA) inner shell, and poly(ethylene oxide) (PEO) corona. First, diblock copolymer PEO-b-PDMA was prepared via the reversible addition-fragmentation chain transfer (RAFT) technique using a PEO-based macroRAFT agent. The dithioester end group of PEO-b-PDMA diblock copolymer was reduced to a thiol end group. The obtained PEO-b-PDMA-SH was then used to prepare diblock copolymer stabilized gold nanoparticles by the "grafting-to" approach. 1,2-Bis(2-iodoethoxy)ethane (BIEE) was utilized to selectively cross-link the PDMA residues in the inner shell. The stimuli responsiveness and colloidal stability of core/shell gold nanoparticles before and after shell cross-linking were characterized by laser light scattering (LLS), UV-vis transmittance, and transmission electron microscopy (TEM). At pH 9, the average hydrodynamic radius Rh of non-cross-linked hybrid gold nanoparticles starts to increase above 35 degrees C due to the lower critical solution temperature (LCST) phase behavior of the PDMA blocks in the inner shell. In contrast, Rh of the shell cross-linked gold nanoparticles were essentially independent of temperature. Core/shell gold nanoparticles before and after shell cross-linking exhibit reversible swelling on varying the solution pH. Compared to non-cross-linked core/shell gold nanoparticles, shell cross-linking of the hybrid gold nanoparticles leads to permanent core/shell nanostructures with much higher colloidal stability and physically isolates the gold core from the external environment.     

MAGfect: a novel liposome formulation for MRI labelling and visualization of cells

Cellular entry of imaging probes, such as contrast agents for magnetic resonance imaging (MRI), is a key requirement for many molecular imaging studies, particularly imaging intracellular events and cell tracking. Here, we describe the successful development and in vitro analysis of MAGfect, a novel liposome formulation containing a lipidic gadolinium contrast agent for MRI, Gd-DOTA-Chol , designed to enter and label cells. Liposome formulation and cell incubation time were optimised for maximum cellular uptake of the imaging probe in a variety of cell lines. MRI analysis of cells incubated with MAGfect showed them to be highly MRI active. This formulation was examined further for cytotoxicity, cell viability and mechanism of cell labelling. One of the key advantages of using MAGfect as a labelling vehicle arises from its potential for additional functions, such as concomitant drug or gene delivery and fluorescent labelling. The gadolinium liposome was found to be an effective vehicle for transport of plasmid DNA (pDNA) into cells and expression levels were comparable to the commercial transfection agent Trojene.     

Thermosensitive pluronic micelles stabilized by shell cross-linking with gold nanoparticles

Gold nanoparticles were employed to prepare shell cross-linked Pluronic micelles that exhibit a reversibly thermosensitive swelling/shrinking behavior. Two terminal hydroxyl groups of Pluronic F127 were thiol-functionalized to form self-assembling Pluronic micelles in aqueous solution with exposed -SH groups in an outer shell layer. The thiol groups present in the outer shell were cross-linked by gold nanoparticles synthesized through NaBH4 reduction of gold precursor anions. The resultant shell cross-linked gold-Pluronic micelles exhibited a temperature-dependent volume transition: their hydrodynamic diameter was changed from 157.1 +/- 15.6 nm at 15 degrees C to 53.4 +/- 5.5 nm at 37 degrees C as determined by dynamic light scattering. The critical micelle temperature measured by a pyrene solubilization technique suggested that the reversible swelling/shrinking behavior of the micelles was caused by hydrophobic interactions of cross-linked or grafted Pluronic copolymer chains in the micelle structure with increasing temperature. Transmission electron microscopy directly revealed that the shell cross-linked micelles were indeed produced by gold nanoparticles covalently clustered on the surface. These novel self-assembled organic/inorganic hybrid micelles would hold great potential for diagnostic and therapeutic applications.     

A vapor selectivity study of microsensor arrays employing various functionalized ligand protected gold nanoclusters

We synthesized and tested four different monolayer protected gold nanoclusters (MPCs) as chemically selective interfaces for an organic vapor sensor array. The ligands chosen for capping the nano-Au particles and for selective organic vapor sorption were octanethiol, 2-naphthalenethiol, 2-benzothiazolethiol and 4-methoxythiolphenol. The same set of gold nanoclusters were tested on two different types of sensor platforms, a chemiresistor (CR) and a quartz crystal microbalance (QCM). The sensing properties of both sensor arrays were investigated with 10 organic vapors of various functional groups. Vapor sensing selectivity, dominated by the shell ligand structure of MPC, was demonstrated. The sensitivities of MPC coated CR are better than those of QCM sensors coated with the same material. The average CR/QCM amplification factors are range from 1.9 for 4-methoxythiolphenol MPC to 16.9 for octanethiol MPC. These differences in amplification factors indicate the functional group specific mechanisms for each vapor-MPC pair. The shell penetration mechanism of hydrogen-bonding vapor molecules into the 2-benzothiazolethiol capped MPC reduced the CR/QCM amplification factors. Strong attraction between MPC shell ligands can also reduce the magnitude of resistance changes during vapor sorption.     

Core/shell quantum dots with high relaxivity and photoluminescence for multimodality imaging

A series of core/shell CdSe/Zn1-xMnxS nanoparticles were synthesized for use in dual-mode optical and magnetic resonance (MR) imaging techniques. Mn2+ content was in the range of 0.6-6.2% and varies with the thickness of the shell or amount of Mn2+ introduced to the reaction. These materials showed high quantum yield (QY), reaching 60% in organic solvent. Water-soluble nanoparticles were obtained by capping the core/shell particles with amphiphilic polymer, and the QY values in water reached 21%. These materials also demonstrated high relaxivity with r1 values in the range of 11-18 mM-1 s-1 (at room temperature, 7 T). Both optical and MR imaging were performed on nanoparticles in aqueous solution and applied to cells in culture. The results showed that the QY and manganese concentration in the particles was sufficient to produce contrast for both modalities at relatively low concentrations of nanoparticles.     

Control of shell thickness in silica-coating of Au nanoparticles and their X-ray imaging properties

This paper describes a performance of precise control of shell thickness in silica-coating of Au nanoparticles based on a sol-gel process, and an investigation into X-ray imaging properties for the silica-coated Au (Au/SiO(2)) particles. The Au nanoparticles with a size of 16.9±1.2 nm prepared through a conventional citrate reduction method were used as core particles. The Au nanoparticles were silica-coated with a sol-gel reaction using tetraethylorthosilicate (TEOS) as a silica source, sodium hydroxide (NaOH) as a catalyst, and (3-aminopropyl) trimethoxysilane (APMS) as a silane coupling agent. An increase in TEOS concentration resulted in an increase in shell thickness. Under certain concentrations of Au, H(2)O, NaOH, and APMS, the Au/SiO(2) particles with silica shell thickness of 6.0-61.0 nm were produced with varying TEOS concentration. Absorption peak wavelength of surface plasmon resonance of the Au/SiO(2) colloid solution depended on silica shell thickness, which agreed approximately with the predictions by Mie theory. The as-prepared colloid solution could be concentrated up to an Au concentration of 0.19 M with salting-out and centrifugation. The concentrated colloid solution showed an X-ray image with high contrast, and a computed tomography value for the colloid solution with an Au concentration of 0.129 M was achieved 1329.7±52.7 HU.     

具有温度响应壳层的金纳米粒子的制备

利用可逆-加成断裂链转移聚合得到全亲水性的嵌段共聚物(PEO-b-PNIPAM), 通过"grafting to"使其接枝到金纳米粒子表面. 通过透射电子显微镜、 紫外-可见吸收光谱、 能谱分析及动态光散射研究了杂化的金纳米粒子的壳层结构及温度响应行为. 实验结果表明, 得到核壳结构的金纳米粒子, 同时其壳层具有温度响应行为. 随着温度的升高, 其流体力学半径略有减小. 在整个升温过程中, 由于外层PEO链段的抑制作用, 没有发生粒子间的聚集.     

Microwave synthesis of core-shell gold/palladium bimetallic nanoparticles

The microwave-assisted polyol reduction method was applied to the synthesis of core-shell gold/palladium bimetallic nanoparticles by the simultaneous reduction of the AuIII and PdII ions. The thickness of the palladium shell was calculated to be approximately 3 nm, and the gold core diameter is 9 nm. The structure and composition of the bimetallic particles were characterized by high-resolution transmission electron microscopy equipped with a nanoarea energy-dispersive X-ray spectroscopy attachment, transmission electron microscopy, X-ray diffraction, and X-ray photoelectron spectroscopy.