Localization Of Gold Nanoparticles Research Articles

Background-free four-wave mixing microscopy of small gold nanoparticles inside a multi-cellular organ

The ability to detect small metallic nanoparticles by optical microscopy inside environmentally relevant species may have a wide impact for ecotoxicology studies. Here, we demonstrate four-wave mixing microscopy on individual small gold nanoparticles inside the hepatopancreas of Oniscus Asellus, a terrestrial isopod, which ingests metals found in the soil. After the exposure to food containing 10 nm radius gold nanoparticles, hepatopancreas tubules were collected, and nanoparticles were imaged by four-wave mixing microscopy with high contrast, locating them with sub-cellular resolution in the volume, despite the significant light scattering from these multi-cellular organs. Notably, the ultrafast dynamics of the four-wave-mixing non-linearity of gold nanoparticles resonantly excited and probed at their localized surface plasmon allows them to be distinguished from other metal deposits in the hepatopancreas, which manifest as a long-lived photothermal contrast. Our findings bring unexpected insight into the location of gold nanoparticles in relation to the cell types forming the hepatopancreas. Considering its simplicity, volumetric imaging capabilities, specificity, and compatibility with living cell studies, four-wave mixing microscopy holds great potential to investigate the fate of metal nanoparticles inside biological systems.

Image-Based Quantification of Gold Nanoparticle Uptake and Localization in 3D Tumor Models to Inform Radiosensitization Schedule.

Gold nanoparticles (GNPs) have shown particular promise as radiosensitizing agents and as complementary drug delivery agents to improve therapeutic index in cancer treatment. Optimal implementation, however, depends critically on the localization of GNPs at the time of irradiation, which, in turn, depends on their size, shape, and chemical functionalization, as well as organism-level pharmacokinetics and interactions with the tumor microenvironment. Here, we use in vitro 3D cultures of A549 lung carcinoma cells, which recapitulate interaction with extracellular matrix (ECM) components, combined with quantitative fluorescence imaging to study how time-dependent localization of ultrasmall GNPs in tumors and ECM impacts the degree of damage enhancement to tumor cells. Confocal imaging of fluorescence-labeled GNPs in 3D culture reveals that nanoparticles are initially embedded in ECM and only gradually accumulate in cancer cells over multiple days. Furthermore, the timing of GNP redistribution from ECM to cellular compartments directly impacts efficacy, with major damage enhancement when irradiation is performed after GNPs have accumulated significantly in 3D tumor nodules. These results underscore the importance of the timing and scheduling in treatment planning to ensure optimal radiosensitization, as well as the necessity of studying these effects in model systems that recapitulate elements of tumor microenvironment interaction.

Compton Background Elimination for in Vivo X-Ray Fluorescence Imaging of Gold Nanoparticles Using Convolutional Neural Network

This article reports the first application of a convolutional neural network (CNN) to in vivo X-ray fluorescence (XRF) images of gold nanoparticles (GNPs) obtained by a benchtop X-ray system to eliminate Compton-scattered photons. The XRF imaging system comprises a 2-D cadmium zinc telluride (CZT) gamma camera, a pinhole collimator, and fan-beam polychromatic X-rays. An architecture of the 2-D CNN model for Compton background elimination was optimally designed and trained with data sets obtained by the measurements of water only and GNP-embedded imaging phantoms. The XRF images generated by the trained 2-D CNN were compared with those generated by the direct subtraction method. The developed 2-D CNN was also applied to generate in vivo XRF images of gold in living mice exposed to GNPs. The in vivo XRF images generated by the two methods were then compared in terms of the difference in GNP concentrations. The results demonstrate that the 2-D CNN model was successfully applied to in vivo XRF images for detecting the concentration and location of GNPs in living mice. This also implies that in vivo XRF images can be acquired using the 2-D CNN without preinjection scanning; thus, the image acquisition time and imaging dose can be reduced by half. Furthermore, in vivo XRF images of GNPs can be acquired at any time after the injection, as the 2-D CNN eliminates the need to restrict a living object during the interscans.

Development and characterisation of a confocal detection array for K-lines of heavy metals in big light matrix

In this work we describe and simulate a setup which allows the X-ray Fluorescence (XRF) detection of gold nanoparticles (GNPs) excited by a convergent orthovoltage X-ray source, immersed in a big matrix of light elements (water). Under these conditions the problem is the poor Signal-to-Noise Ratio (SNR), which under normal irradiation conditions limit the detection of the GNPs.For the X-ray source (Teledyne CP120B) multiple calculations using SpekCalc software were run to determine an optimum external filtering thickness and collimation material, where was found that 1 mm of Cu external filtering improves the ratio and quantity of useful photons above the Au K-edge absorption energy. Monte Carlo (PENELOPE v2008) simulations were performed using the confocal geometry. The scenarios, including the composition (lead and bronze alloys), shape (cylindrical, conical) and location of the detectors were defined. Using a set of combinations for collimators in the X-ray source and detectors, where both are aligned to a unique focal point, it was possible to increase the SNR of the XRF signal with respect to Compton radiation in a specific region within the phantom, which makes possible to identify the location of the GNPs. The best SNR (185%) was achieved using a 4 cm length conical collimator made of lead.This would allow the development of a new technique for functional medical imaging, and according with the outcome of these simulations, in subsequent stages a prototype will be developed to validate the simulation outcomes, and confirm that it is possible to detect the location of GNPs from a human scale phantom based on their fluorescent emission.

On the importance of modeling gold nanoparticles distribution in dose-enhanced radiotherapy.

Purpose: To investigate the effect of precise modeling for Monte Carlo simulations of gold nanoparticles (GNPs) dose-enhanced radiotherapy, two models characterized by their distribution of GNPs in a simulated macroscopic cubic tumor were introduced. The motivation was the widely documented tendency of GNPs to localize around the cell nucleus.Methods: The introduced models composed of 2.7×107 ellipsoid cells, each of them containing a centrally located nucleus as the target for dose evaluation. In the first model, the spheres of GNP are homogeneously distributed in the whole tumor volume, and in the latter, GNPs are localized in the cytoplasms surrounded the nuclei.Results: The results achieved through applying Monte Carlo radiation transports using the Mont Carlo N-Particle eXtended code (MCNPX) show an underestimation of nuclear dose enhancement caused by homogeneous model compared with that of heterogeneous distribution. By investigating various quantities, it was found that subcellular location of GNPs strongly governs the sensitivity of dose enhancement to the number and concentration of GNPs targeted in the tumor. Other obvious differences are revealed by studying the dose enhancement curves in depth of the tumor. While the heterogeneous model predicts an approximately constant dose enhancement in depth for primary photon energies of 50 keV and more, the homogeneous model estimates an energy-dependent increase of about 11 to 30%.Conclusion: It can be concluded that defining a model in accordance with the experimental observations can effectively account for accurate prediction of macroscopic dose enhancement in the target of interest.

Nanogold-Gallate Chitosan-Targeted Pulmonary Delivery for Treatment of Lung Cancer.

Lung cancer is one of the most of cancer type founds and a leading cause of death worldwide. Through the development of new candidate compound (3,4,5-tribenzyloxybenzoic acid (GAOBn)) and a drug delivery system of our design of quaternized chitosan-gallic acid-folic acid stabilized gold nanoparticles (Au@QCS-GA-FA) as the targeted nanocarrier for treatment of lung cancer, we have found that GAOBn not only showed high cytotoxicity against lung cancer cells (CHAGO) with more than tenfold than cisplatin, but also showed low toxicity against normal cells (CRL-1947). The combination Au@QCS-GA-FA/GAOBn showed highly efficient cellular uptake and localization of gold nanoparticles via the active targeting of cancer cells. This established the potential of Au@QCS-GA-FA as a nanocarrier for anticancer agent-targeted delivery for treatment of lung cancer.

Perylene Derivative Dyes Luminescence in Polysiloxane Matrix in Presence of Gold Nanoparticles.

Four perylene derivatives, including commercially available dyes Lumogen Red and Lumogen Orange, as well as 1,6,7,12-tetrachlоrоperylene-3,4,9,10-tetradicarboxydianhydride (Dye I) and 3,4:9,10-bis(1,2-benzimidazole)- 1,6,7,12-tetra(4-tert-octylphenoxy) perylene (syn/ anti-isomers) (Dye III, which was prepared from dye I through intermediate 3,4:9,10-bis(1,2-benzimidazole)-1,6,7,12-tetrachloro perylene (Dye II)) were used for preparation of polysiloxane samples (PSi) containing different concentrations of gold nanoparticles (GN). Dyes I and III demonstrate significant fluorescence intensity increase upon addition of GN independent on excitation energy. For Lumogen Red composition in PSi some increase of fluorescence intensity was observed upon addition of small concentrations of GN, while further increase of GN concentration quenches fluorescence. The increase of Lumogen Red emission intensity, which depends on energy of excitation, is probably due to the increase of radiation decay rate since excitation rate decreases. Effect of GN on Lumogen Orange provided quenching of fluorescence even at small concentrations of GN. Calculations at DFT level of approximation for dye III suggest location of GN in plane of perylene core for increase of fluorescence intensity.

Identification and Localization of Gold Nanoparticles in Potassium Ion Pores: Implications for Kir Blockade.

IntroductionIn our previous study, we found that negatively charged gold nanoparticles with spermidine have the potential of blocking inwardly rectifying potassium channels (Kir), both at the cellular and the tissue level.MethodsFor the purpose of the present study, we purified the cytoplasmic domain of the Kir 3.1 receptor from Escherichia coli. Using single particles with surface coating by transmission electron microscopy, we identified the gold nanoparticles at the cytoplasmic side of the human Kir channel.ResultsEnergy-dispersive X-ray spectroscopy showed the presence of the gold deposits in the cytoplasmic domain of the Kir receptor.ConclusionIn conclusion, we could identify undecagold in the ion pore of the Kir3.1 channel in order to clarify its direct blocking effect in the Kir ion pore by undecagold.Electronic supplementary materialThe online version of this article (doi:10.1007/s40119-016-0060-8) contains supplementary material, which is available to authorized users.

Chromatogram Analysis on Revealing Aggregated Number and Location of Gold Nanoparticles Within Living Cells

We present a method to directly observe three-dimensional (3D) distribution of aggregated gold nanoparticles (Au NPs) in live cells using dark-field sectional optical microscopy with chromatographic analysis. The scattering images of clustered Au NPs were transformed from RGB regular coordinate to hue, saturation, and value (HSV) cylindrical coordinate. The hue distinguished Au NPs from scattering images of cellular organelles. The saturation eliminated the interference from the defocused spots. The value, which indicated the scattering intensity, defined the 3D locations of Au NPs. The V/H ratio showed a linear relation with the Au NP number in the cluster. It was applied to estimate the numbers of aggregated nanoparticles in endosome vesicles. Using the chromatographic analysis, the calculated nanoparticle numbers were in good agreement with mass spectroscopic measurement. Compared to conventional methods, the chromatographic approach provides a simple observation of 3D distribution of Au NPs and their aggregation states in living cells.

Gold nanoaggregates for probing single-living cell based on surface-enhanced Raman spectroscopy.

Gold nanoparticles are delivered into living cells by transient electroporation method to obtain intracellular surface-enhanced Raman spectroscopy (SERS). The subcellular localization of gold nanoparticles is characterized by transmission electron microscopy, and the forming large gold nanoaggregates are mostly found in the cytoplasm. The SERS detection of cells indicates that this kind of gold nanostructures induces a high signal enhancement of cellular chemical compositions, in addition to less cellular toxicity than that of silver nanoparticles. These results demonstrate that rapid incorporation of gold nanoparticles by electroporation into cells has great potential applications in the studies of cell biology and biomedicine.

Plasmonic effect of gold nanoparticles in organic solar cells

Light trapping, due to the embedding of metallic nanoparticles, has been shown to be beneficial for a better photoabsorption in organic solar cells. Researchers in plasmonics and in the organic photovoltaics fields are working together to improve the absorption of sunlight and the photon–electron coupling to boost the performance of the devices.Recent advances in the field of plasmonics for organic solar cells focus on the incorporation of gold nanoparticles. This article reviews the different methods to produce and embed gold nanoparticles into organic solar cells. In particular, concentration, size and geometry of gold nanoparticles are key factors that directly influence the light absorption in the devices. It is shown that a careful choice of size, concentration and location of gold nanoparticles in the device result in an enhancement of the power conversion efficiencies when compared to standard organic solar cell devices.Our latest results on gold nanoparticles embedded in on organic solar cell devices are included. We demonstrate that embedded gold nanoparticles, created by depositing and annealing a gold film on transparent electrode, generate a plasmonic effect which can be exploited to increase the power conversion efficiency of a bulk heterojunction solar cell up to 10%.

Efficient Internalization and Intracellular Translocation of Inhaled Gold Nanoparticles in Rat Alveolar Macrophages

To investigate the relationship of alveolar macrophages and inhaled nanoparticles (NPs) in the lung. Rats were exposed by inhalation to 16-nm gold NPs for 6 h, and ultramicroscopic observation on the frequency and localization of gold NPs within lavaged macrophages was performed for 7 days. The majority of macrophages examined on day 0 (94%) contained internalized gold NPs, and the percentage decreased to 59% on day 7. Gold NPs were exclusively found within cytoplasmic vesicles. On day 0, most gold NPs appeared to be individual or slightly agglomerated, while they were frequently agglomerated on day 7. Alveolar macrophages efficiently internalized NPs by endocytosis, and rearrangements of vesicles and of NPs in the vesicles of macrophages occurred.

Photoluminescence spectroscopy and lifetime measurements from self-assembled semiconductor-metal nanoparticle hybrid arrays

We present results of photoluminescence spectroscopy and lifetime measurements on thin film hybrid arrays of semiconductor quantum dots and metal nanoparticles embedded in a block copolymer template. The intensity of emission as well as the measured lifetime would be controlled by varying the volume fraction and location of gold nanoparticles in the matrix. We demonstrate the ability to both enhance and quench the luminescence in the hybrids as compared to the quantum dot array films while simultaneously engineering large reduction in luminescence lifetime with incorporation of gold nanoparticles.

The location of gold nanoparticles on titania: A study by high resolution aberration-corrected electron microscopy and 3D electron tomography

Using HAADF-STEM electron tomography and aberration-corrected TEM/STEM electron microscopy, 3D reconstructions and high resolution images have been recorded of heterogeneous catalysts consisting of gold nanoparticles supported on titanium dioxide (anatase); these catalysts have gained attention recently because of their potential for use in many reactions with both industrial and environmental importance. We will illustrate how through the combination of high resolution images and segmented 3D tomographic data, structural features of the supported phase can be revealed which are normally not accessible through conventional imaging. The location of the nanoparticles preferentially at the grain boundaries, confirmed by these studies, is likely to influence the stability of the nanoparticles and is a key step in understanding and facilitating the development of better catalysts.

Nuclear Targeting of Gold Nanoparticles in Cancer Cells Induces DNA Damage, Causing Cytokinesis Arrest and Apoptosis

By properly conjugating gold nanoparticles with specific peptides, we were successful in selectively transporting them to the nuclei of cancer cells. Confocal microscopy images of DNA double-strand breaks showed that localization of gold nanoparticles at the nucleus of a cancer cell damages the DNA. Gold nanoparticle dark-field imaging of live cells in real time revealed that the nuclear targeting of gold nanoparticles specifically induces cytokinesis arrest in cancer cells, where binucleate cell formation occurs after mitosis takes place. Flow cytometry results indicated that the failure to complete cell division led to programmed cell death (apoptosis) in cancer cells. These results show that gold nanoparticles localized at the nuclei of cancer cells have important implications in understanding the interaction between nanomaterials and living systems.

Interaction of gold nanoparticles with mitochondria

Mitochondrion is one of the most important organelles in cells with several vital responsibilities. The consequence of a deficiency in the function of mitochondrion could result with the wide range of diseases and disorders. In this study, we investigated the feasibility of utilizing surface-enhanced Raman scattering (SERS) to understand the mode of interaction of gold nanoparticles (GNPs) with mitochondria. The living lung cancer cells and the isolated mitochondria from these cells were treated with gold colloidal suspension for SERS experiments. The AFM images of the mitochondria confirmed that the treatment did not cause substantial damage to mitochondria. The localization of GNPs in living cells is investigated with confocal microscopy and found that GNPs form aggregates in the cytosol away from the mitochondria. However, SERS spectra obtained from isolated mitochondria and living cells indicate that GNPs escaped from the endosomes or entered into the living cell through another route may be in contact with mitochondria in a living cell. The findings of this study indicate that SERS can be used for mitochondrial research.

In vitro permeation of gold nanoparticles through rat skin and rat intestine: Effect of particle size

Purpose of the present work was to study in vitro permeation of gold nanoparticles (NPs) through isolated rat skin and intestine. Another objective was to see the effect of particle size on permeation of the gold NP. Gold NP of 15 nm, 102 nm and 198 nm were synthesized and used for study. Franz diffusion cells were used to evaluate permeation of gold NP from rat skin whereas ‘intestinal sac’ method was used for assessing intestinal permeation. Number density of gold NP was analyzed by UV–vis spectroscopy whereas amount of gold permeated was measured by ICP mass spectrometry. The absorption and localization of gold NP through rat skin was studied by TEM. Qualitative analysis of gold inside of the rat skin was performed by energy dispersive X-ray spectroscopy (EDS). Gold NP showed negative zeta potential. UV–vis absorption spectra of 15 nm, 102 nm and 198 nm gold NP showed λ max at 520 nm, 535 nm and 577 nm, respectively. SEM study revealed spherical morphology of NP. Gold NP showed size dependent permeation through rat skin and intestine. 15 nm gold NP showed higher permeation compared to 102 nm and 198 nm gold NP. Interestingly, 102 nm and 198 nm gold NP showed lag time of 3 h and 6 h in case of rat skin only. As the size of the gold NP increased, permeability coefficient and diffusion coefficient was found to be decreased. The permeation of gold NP through intestine was higher than that of skin. TEM study of rat skin revealed accumulation of smaller size gold NP in deeper region of skin whereas larger particles were observed mainly in epidermis and dermis. Presence of gold inside of rat skin was confirmed by EDS. Gold NP would be an interesting carrier for transdermal as well as for oral delivery. The study demonstrated initial proof of concept of percutaneous permeation of smaller size gold particles.