Hybrid gold nanoparticles in molecular imaging and radiotherapy

Metallic nanoparticles, because of their size, chemical and physical properties, are particularly attractive as therapeutic probes in treating cancer. Central to any clinical advances in nanoparticulate based therapy will be to produce hybrid nanoparticles that can be targeted to vascular, extracellular or cell surface receptors. Development of hybrid nanoparticles that specifically target cancer vasculature has received considerable attention. Most cancers have leaky vasculature and the defective vascular architecture, created due to the rapid vascularization necessary to serve fast growing cancers, in combination with poor lymphatic drainage allows increased permeation and retention effects. The leaky vasculature, because of higher porosity and permeability, serve as natural high affinity targets to metallic nanoparticles. Another attractive approach toward the application of nanotechnology to nanomedicine is the utility of nanoparticles that display inherent therapeutic properties. For example radioactive gold nanoparticles present attractive prospects in therapy of cancer. The radioactive properties of Au-198 (β_max=0.96 MeV; t_1/2=2.7 d) and Au-199 (β_max=0.46 MeV; t_1/2=3.14 d) make them ideal candidates for use in radiotherapeutic applications. In addition, they both have imageable gamma emissions for dosimetry and pharmacokinetic studies and Au-199 can be made carrier-free by indirect methods. Gold nanoparticles are of interest for treatment of disease as they can deliver agents directly into cells and cellular components with a higher concentration of radioactivity, e.g. higher dose of radioactivity, to cancerous tumor cells.     

Tomographic molecular imaging of x-ray-excitable nanoparticles

X-ray luminescence computed tomography (XLCT) is proposed as a new dual molecular/anatomical imaging modality. XLCT is based on the selective excitation and optical detection of x-ray-excitable nanoparticles. As a proof of concept, we built a prototype XLCT system and imaged near-IR-emitting Gd(2)O(2)S:Eu phosphors in various phantoms. Imaging in an optically diffusive medium shows that imaging performance is not affected by optical scatter; furthermore, the linear response of the reconstructed images suggests that XLCT is capable of quantitative imaging.     

金纳米棒核／二氧化硅壳纳米复合结构的可控制备及细胞成像

采用模板合成以及溶胶凝胶方法制备了金纳米棒核／二氧化硅壳（GNR@SiO2）纳米复合粒子,探讨了这种新型纳米复合结构的可控制备、光谱性质、细胞毒性和细胞成像。通过紫外可见分光光度计、透射电镜、共聚焦显微镜对样品进行表征,结果表明：通过对反应时间的调控,获得的纳米复合粒子的二氧化硅壳层厚度可以控制在20～30nm。由于二氧化硅壳层的存在,大大提高了金纳米棒的稳定性,同时降低了金纳米棒的细胞毒性;此外,由于二氧化硅壳层具有良好的化学修饰作用,因此可以将荧光探针分子标记在二氧化硅壳层表面,修饰后的纳米复合粒子可以通过细胞内吞作用进入细胞,从而实现细胞内的光学成像。因此,该纳米粒子复合材料在生物传感、细胞成像以及光热治疗等方面有着良好的应用前景。     

Plasmon-resonant gold nanoparticles for cancer optical imaging

Gold nanoparticles(AuNPs) interact with light and have strong and tunable surface plasmon resonance,which can be detected using multiple imaging modalities.These provide an unique opportunity for their potential applications in optical imaging for early detection of cancer.In this review,we summarized nanoparticles targeting properties for cancer,plasmon optical properties of AuNPs,application of AuNPs for cancer optical imaging.Also discussed is the safety of AuNPs.     

Two-photon imaging of lymphoma cells targeted by gold nanoparticles

Gold nanoparticles (NPs) have highly efficient multi-photon-induced luminescence. In this paper, we record the two-photon images of gold NPs, lymphoma cell line Karpas 299, and Karpas 299 incubated with 30-nm-diameter gold NPs and ACT-1 antibody conjugates (Au30-ACT-1 conjugates) by using a multi-photon microscopy system. Due to the specific conjugation of ACT-1 antibody and celt membrane receptor CD25, gold NPs are only bound to the surface of cell membrane of Karpas 299. The luminescence intensity of gold NPs is higher than that of cells at 750-nm laser excitation. By comparing the images of Karpas 299 cells incubated with and without gold NPs, it is found that by means of gold NPs, we can get clear cell images with lower excitation power. Their excellent optical and chemical properties make gold NPs an attractive contrast agent for cellular imaging.     

Subdiffraction scattered light imaging of gold nanoparticles using structured illumination

A reflective light-scattering (RLS) microscope with structured illumination (SI) provides subdiffraction resolution and improves the image quality of gold nanoparticles in biological systems. The three-dimensional (3D)-structured pattern is rapidly and precisely controlled with a spatial light modulator and scrambled at the conjugate image plane to increase spatial incoherence. The reconstructed SI-RLS image of 100?nm gold nanoparticles reveals lateral and axial resolutions of approximately 117 and 428?nm. We present a high-resolution image of gold nanoparticles inside a HeLa cell, with improved contrast.     

Molecular wires and gold nanoparticles as molewares for the molecular scale electronics

The continuing shrinkage of the feature sizes in microelectronics requests the use of nanolithographic technology that causes the exponential increase of cost in building the fabrication facility. Molecules can be synthesized in precisely controlled way to have nano-structures in large quantities, utilizing molecules as electronic components in the nanoelectronic circuitry may be one promising alternative of manufacturing high density chips in more affordable prices. The molecular scale electronics research has shown that molecules can be good conductors and molecular switch can be used succesfully to modulate the flow of electrons. Some of the recent progresses in molecular scale electronics are reviewed and the use of modified gold nanoparticles to assemble the devices is introduced.     

Anisotropic gold nanoparticles and gold plates biosynthesis using alfalfa extracts

Industrial and medical applications for gold nanoparticles are extensive, yet highly dependent on their chemical and structural properties. Thus, harnessing the size and shape of nanoparticles plays an important role in nanoscience and nanotechnology. Anisotropic polyhedra and nanoplates were biosynthesized via reduction of 3 mM AuCl₄ ⁻ solution at room temperature. Alfalfa biomass extracts prepared in water and in isopropanol separately were used as reducing agents at pH 3.5 and 3.0, respectively. Nanoparticles observed in the isopropanol extract presented a size range of 30–60 nm, and the morphologies present included 30 nm decahedra and 15 nm icosahedra. Gold nanoplates produced in the water extract were mainly triangular, ranging from 500 nm to 4 μm in size. The resulting nanoparticles and nanoplates can be potentially used in the study of their unique physical properties and for the mechanisms of formation using alfalfa biomass extracts.     

GoldMag nanoparticles with core/shell structure: characterization and application in MR molecular imaging

GoldMag is a kind of bi-functional nanoparticle, composed of a gold nanoshell and an iron oxide core. GoldMag combines the antibody immobilization property of gold nanoshell with the superparamagnetic feature of the iron oxide core. Rabbit anti-mouse IgG was immobilized on the surface of GoldMag to synthesize GoldMag-IgG in a single-step process. Transmission electron microscopy, UV/Vis spectrophotometry, zeta potential analysis, dynamic light scattering, enzyme-linked immunosorbent assay, and magnetic resonance imaging (MRI) were employed to characterize the nanostructures and the spectroscopic and magnetic properties of GoldMag and GoldMag-IgG. The antibody encapsulation efficiency of GoldMag was measured as 58.7%, and the antibody loading capacity was 88 μg IgG per milligram of GoldMag. The immunoactivity of GoldMag-IgG was estimated to be 43.3% of that of the original IgG. The cytotoxicity of GoldMag was assessed by MTT assay, which showed that it has only little influence on human dermal lymphatic endothelial cells. MR imaging of different concentrations of ultrasmall superparamagnetic iron oxide, GoldMag, and GoldMag-IgG showed that 3 μg/mL of nanoparticles could significantly affect the MRI signal intensity of GRE T2*WI. The results demonstrate that GoldMag nanoparticles can be effectively conjugated with biomacromolecules and possess great potential for MR molecular imaging.     

Size- and temperature-dependent structural transitions in gold nanoparticles

Size- and temperature-dependent structural transitions in gold nanoparticles were revealed with morphology statistics obtained by high-resolution electron microscopic observations for thousands of particles annealed in a helium heat bath. We found that gold nanoparticles over a wide size range, 3-14 nm, undergo a structural transformation from icosahedral to decahedral morphology just below the melting points. It was also clarified that the formation of bulk crystalline structures from the decahedral morphology requires the melt-freeze process due to an insurmountable high free-energy barrier.     

Shape evolution of gold nanoparticles

The tetraoctylammonium bromide-stabilized gold nanoparticles have been successfully fabricated. The shape evolution of these nanoparticles under different annealing temperatures has been investigated using high-resolution transmission electron microscopy. After an annealing at 100 °C for 30 min, the average diameters of the gold nanoparticles change a little. However, the shapes of gold nanoparticles change drastically, and facets appear in most nanoparticles. After an annealing at 200 °C for 30 min, not only the size but also the shape changes a lot. After an annealing at 300 °C for 30 min, two or more gold nanoparticles coalesce into bigger ones. In addition, because of the presence of Cu grid during the annealing, some gold particles become the nucleation sites of Cu₂O nanocubes, which possess a microstructure of gold-particle core/Cu₂O shell. These Au/Cu₂O heterostructure nanocubes can only be formed at a relatively high temperature (≥300 °C). The results can provide some insights on controlling the shapes of gold nanoparticles.     

Ripening of nanowire-supported gold nanoparticles

Gold nanoparticles have applications ranging from catalysts for low temperature oxidation of CO to solar energy capture in the infrared. For all these applications, particle size and shape are critical. In this study, nanoparticle gold formed on GaN nanowires by plasma-enhanced chemical vapor deposition was annealed at temperatures ranging from 150 to 270 °C for 24 h. Particle size was measured before and after annealing using a field emission scanning electron microscope. Ripening of the gold particles was observed even at the lowest annealing temperatures of the study. The particle growth kinetics showed an Arrhenius relationship with activation energy of 27.38 kJ/mol. This value suggests that ripening occurs by particle migration and coalescence rather than adatom diffusion.     

Solidification of gold nanoparticles in carbon nanotubes

The structure and the solidification of gold nanoparticles in a carbon nanotube are investigated using molecular dynamics simulations. The simulations indicate that the predicted solidification temperature of the enclosed particle is lower than its bulk counterpart, but higher than that observed for clusters placed in vacuum. A comparison with a phenomenological model indicates that, in the considered range of tube radii (R(CNT)) of 0.5 < R(CNT) < 1.6 nm, the solidification temperature depends mainly on the length of the particle with a minor dependence on R(CNT).     

Quantum spins in Mackay icosahedral gold nanoparticles

We report on the direct observation of the intrinsic magnetization behavior of Mackay icosahedral Au nanoparticles. The spin arrangements in 3.5-nm icosahedral Au particles are found to be ferrimagnetic-like, where the core and surface moments point in opposite directions, with a net spontaneous magnetic moment of 16 μ_B per particle. The unpaired spins behave as J = 1/2 quantum spins. The average level separation is found to be a factor of ~1.53 larger than that estimated according to the Kubo formula for spherical Au particles. This reflects the fact that there are considerably fewer atoms packed in a particle with an icosahedral geometry than with a spherical one.     

Trapping and release of citrate-capped gold nanoparticles

An electrical method to trap and release charged gold nanoparticles onto and from the surface of gold electrodes modified by an alkanethiol self-assembled monolayer (SAM) is presented. To form electrodes coated with gold nanoparticles (GNPs), amine-terminated SAMs on gold electrodes were immersed in a solution of negatively charged citrate-capped GNPs. Accumulation of GNPs on the electrode surface was monitored by a decrease in the impedance of the SAM-modified electrode and by an increase in the electrochemical activity at the electrode as shown through cyclic voltammetry (CV). Electrostatic interactions between the GNPs and the amine-terminated SAM trap the GNPs on the electrode surface. Application of a subsequent negative bias to the electrode initiated a partial release of the GNPs from the electrode surface. Impedance spectroscopy, cyclic voltammetry, ultraviolet-visible (UV-Vis) spectroscopy and atomic force microscopy (AFM) were used to monitor and confirm the attraction of GNPs to and release from the aminealkanethiolated gold electrodes. This work describes a method of trapping and release for citrate-capped GNPs that could be used for on-demand nanoparticle delivery applications such as in assessing and modeling nanoparticle toxicology, as well as for monitoring the functionalization of gold nanoparticles.     

Monofunctional gold nanoparticles: synthesis and applications

The ability to control the assembly of nanoparticle building blocks is critically important for the development of new materials and devices. The properties and functions of nanomaterials are not only dependent on the size and properties of individual particles, but also the interparticle distance and interactions. In order to control the structures of nanoassemblies, it is important to first achieve a precise control on the chemical functionality of nanoparticle building blocks. This review discusses three methods that have been reported recently for the preparation of monofunctional gold nanoparticles, i.e., nanoparticles with a single chemical functional group attached to each particle. The advantages and disadvantages of the three methods are discussed and compared. With a single functional group attached to the surface, one can treat such nanoparticles as molecular building blocks to react with other molecules or nanoparticles. In other words, by using appropriate chemical reactions, nanoparticles can be linked together into nanoassemblies and materials by covalent bonds, similar to the total chemical synthesis of complicated organic compounds from smaller molecular units. An example of using this approach for the synthesis of nanoparticle/polymer hybrid materials with optical limiting properties is presented. Other potential applications and advantages of covalent bond-based nanoarchitectures vs. non-covalent interaction-based supramolecular self-assemblies are also discussed briefly in this review.     

Improved signal processing to detect cancer by ultrasonic molecular imaging of targeted nanoparticles

In several investigations of molecular imaging of angiogenic neovasculature using a targeted contrast agent, Renyi entropy [I(f)(r)] and a limiting form of Renyi entropy (I(f,∞)) exhibited significantly more sensitivity to subtle changes in scattering architecture than energy-based methods. Many of these studies required the fitting of a cubic spline to backscattered waveforms prior to calculation of entropy [either I(f)(r) or I(f,∞)]. In this study, it is shown that the robustness of I(f,∞) may be improved by using a smoothing spline. Results are presented showing the impact of different smoothing parameters. In addition, if smoothing is preceded by low-pass filtering of the waveforms, further improvements may be obtained.     

Laser-based transfection with conjugated gold nanoparticles

The irradiation of ceils combined with the immunoconjugate of gold nanoparticles by the short pulse laser can make the plasma membrane be transiently permeabilized, which can be used to transfer exogenous molecules into the cells. We explore this technique as a novel gene transfection method for floating cells. Three different floating cells exposed to the laser are selectively transfected with fluorescein isothiocyanatedextran, antibody, and green fluorescent protein （GFP） coding plasmids, and the viability of cells are determined by propidium iodide. For fluorescein isothiocyanate-dextran, the best transfection efficiency of 65% is obtained; for the antibody, it is 74%; whereas for the green fluorescent protein coding plasmids, a very small transfection efficiency is gained. If the transfection efficiency is improved, gold nanoparticles will be very useful as mediator for gene transfection in living cells.     

Agglomeration behavior of lipid-capped gold nanoparticles

The current investigation deciphers aggregation pattern of gold nanoparticles (AuNPs) and lipid-treated AuNPs when subjected to aqueous sodium chloride solution with increasing ionic strengths (100–400 nM). AuNPs were synthesized using 0.29 mM chloroauric acid and by varying the concentrations of trisodium citrate (AuNP1 1.55 mM, AuNP2 3.1 mM) and silver nitrate (AuNP3 5.3 μM, AuNP4 10.6 μM) with characteristic LSPR peaks in the range of 525–533 nm. TEM analysis revealed AuNPs to be predominantly faceted nanocrystals with the average size of AuNP1 to be 35?±?5 nm, AuNP2 15?±?5 nm, AuNP3 30?±?5 nm, and AuNP4 30?±?5 nm and the zeta-average for AuNPs were calculated to be 31.23, 63.80, 26.08, and 28 nm respectively. Induced aggregation was observed within 10 s in all synthesized AuNPs while lipid-treated AuNP2 (AuNP2-L) was found to withstand ionic interferences at all concentration levels. However, lipid-treated AuNPs synthesized using silver nitrate and 1.55 mM trisodium citrate (AuNP3, AuNP4) showed much lower stability. The zeta potential values of lipid-treated AuNPs (AuNP1-L-1x/200, ??17.93?±?1.02 mV; AuNP2-L-1x/200, ??21.63?±?0.70; AuNP3-L-1x/200, ??14.54?±?0.90; AuNP3-L-1x/200 ??13.77?±?0.83) justified these observations. To summarize, AuNP1 and AuNP2 treated with lipid mixture 1 equals or above 1x/200 or 1x/1000 respectively showed strong resistance against ionic interferences (up to 400 mM NaCl). Use of lipid mixture 1 for obtaining highly stable AuNPs also provided functional arms of various lengths which can be used for covalent coupling.

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Graphical abstract Agglomeration behavior of gold nanoparticles before and after lipid capping

     

Photochemical synthesis of polygonal gold nanoparticles

In this paper, we propose a method to generate gold nanoparticles capable of absorbing near infrared light (NIR) radiation through a photochemical reaction. This approach does not require the use of either surfactants or polymers, reducing the difficulties that may arise in further chemical modifications for the gold nanoparticles. The gold nanoparticles with either triangular or hexagonal shapes were generated using the photo-reduction method, mixing hydrogen tetrachloroaurate with sodium oxalate, a reducing agent, in aqueous solution under illumination of a mercury lamp (λ_max = 306 nm) for more than 10 min. The size of the gold nanoparticles varies from 25 to 200 nm, which mainly depends on the duration of light illumination and the concentration of sodium oxalate. Furthermore, we demonstrate that the presence of the gold nanoparticles in aqueous solutions can effectively elevate the temperature of the solutions under irradiation of NIR light (808 nm) within a few minutes. The gold nanoparticles can be potentially used as suitable photothermal agents for hyperthermia.