Tuning Ultrafast Photoresponse of Gold Nanorods

Nondegenerate pump probe differential transmission experiments on gold nanorods with varying longitudinal surface plasmon resonance have revealed a new phenomenon where the polarity of the transient transmission signal can be reversibly switched between photo bleaching and photo-induced absorption by controlling probe fluence. Under the usual case where probe fluences are nominal, photo bleaching effect is observed for the nanorods with longitudinal surface plasmon resonance energy smaller than the probe photon energy. The laser-induced melting of the nanorods or change in their shape is ruled out for the observed optical switching effect. A quantitative understanding of the results is attempted by invoking a cascaded two-photon absorption dominant beyond a threshold probe fluence of ～75 μJ/cm².     

Enhanced Thermal Stability and Biocompatibility of Gold Nanorods by Graphene Oxide

In the present study, the effect of nanosized graphene oxide layer on thermal stability and biocompatibility of gold nanorods has been examined. The graphene oxide-wrapped gold nanorods were prepared by electrostatic interaction between negatively charged graphene oxide and positively charged nanorods. The resulting nanohybrids were then heated at different time intervals to 95 °C in a water bath to assess the effect of heat on the rods morphology. The structural changes in gold nanorods were monitored via UV-Vis spectroscopy measurements and transmission electron microscopy images. In similar experiments, the graphene oxide used to wrap gold nanorods was reduced by ascorbic acid in a 95 °C water bath. Our results indicate that while bare gold nanorods are highly vulnerable to elevated temperatures, graphene oxide and reduced graphene oxide-coated gold nanorods remain thermally stable with no structural changes. We also confirmed that the enhanced thermal stability is highly dependent on the concentration of deposited graphene oxide available on the surface of the gold nanorods. In addition, we performed an MTT (3-[4,5-dimethylthiazol-2yl]-2,5-diphenyltetrazoliumbromide) assay to make a comparison between the cytotoxicity of the nanohybrids and their primary building blocks on human dermal fibroblast cells as a normal cell line. We found evidence that graphene oxide can enhance the biocompatibility of the rods through covering toxic chemicals on the surface of them.

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Modulation of Optical Properties of Gold Nanorods on Addition of KOH

Gold nanorods are known to exhibit two distinct surface plasmon oscillations namely, transverse and longitudinal bands corresponding to oscillations of conduction electrons along width and length of gold nanorods. Considerable changes in these surface plasmon resonance peak positions occurred when KOH was added to the nanorod solution. Nanorods with initial longitudinal plasmon band at 739, 796, and 895 nm are studied with variation in KOH concentration. While the longitudinal plasmon resonance peak showed blue shift, transverse plasmon resonance peak exhibited only intensity variations. Changes could be attributed to the shape transition of gold nanorods on variation of pH in the solution. Shape transition of gold nanorods is confirmed by transmission electron microscopy images.     

Controlled release of PEG chain from gold nanorods: Targeted delivery to tumor

Gold nanorods exhibit strong absorbance of light in the near infrared region, which penetrates deeply into tissues. Since the absorbed light energy is converted into heat, gold nanorods are expected to act as a contrast agent for in vivo bioimaging and as a thermal converter for photothermal therapy. To construct a gold nanorod targeted delivery system for tumor a peptide substrate for urokinase-type plasminogen activator (uPA), expressed specifically on malignant tumors, was inserted between the PEG chain and the surface of the gold nanorods. In other words, we constructed PEG–peptide-modified gold nanorods. After mixing the gold nanorods with uPA, the PEG chain was released from the surface of the gold and subsequently nanorod aggregation took place. The formation of the aggregation was monitored as a decrease in light absorption at 900 nm. Tumor homogenate induced a significant decrease in this absorption. Larger amount of the PEG–peptide-modified gold nanorods bound to cells expressing uPA in vitro compared with control gold nanorods, which had scrambled sequence of the peptide. The PEG–peptide-modified gold nanorods showed higher accumulation in tumor than the control after they were injected intravenously into tumor-bearing mice, however, the density of the peptide on the surface of the gold nanorods was a key factor of their biodistributions. This targeted delivery system, which responds to uPA activity, is expected to be a powerful tool for tumor bioimaging and photothermal tumor therapy.     

Functionalization of Gold Nanorods Toward Their Applications

The topics focusing on functionalization of gold nanorods have been reviewed with a view toward their advanced uses. In most cases, as-prepared gold nanorods are hydrophilic and protected by surfactants, since anisotropic growth of gold nanorods by chemical, electrochemical, and photo-induced methods is carried out in aqueous media in the presence of surfactants and additives. Since solvophilicity of gold nanorods predominantly affects on their optical properties, the control of dispersity of gold nanorods in matrices has been performed, without loss of their optical characters, by surface modification and hybridization with small molecules or polymers. As a result of the functionalization procedure, the capability of self-assembly of gold nanorods has been improved. Furthermore, the examples of application using gold nanorods demonstrate that gold nanorod is a promising material.     

金纳米棒的光学性质及其在生物医学领域的应用

简要介绍金纳米棒的光学性质和合成方法,重点阐述其在生物医学领域研究的最新进展,并对其今后的研究方向进行展望．金纳米棒是一种胶囊状的金纳米颗粒,具有一个横向等离子共振吸收峰和一个纵向等离子共振吸收峰,分别对应其横轴和纵轴两个特征尺寸．通过调节金纳米棒的长径比,纵向等离子共振吸收峰可由可见光区跨越至近红外光区．金纳米棒这一独特的光学性质在生物和化学传感方面有着广泛而重要的应用前景．     

Nanostructure shape effects on response of plasmonic aptamer sensors

A localized surface plasmon resonance (LSPR) sensor surface was fabricated by the deposition of gold nanorods on a glass substrate and subsequent immobilization of the DNA aptamer, which specifically bind to thrombin. This LSPR aptamer sensor showed a response of 6‐nm λ_max shift for protein binding with the detection limit of at least 10 pM, indicating one of the highest sensitivities achieved for thrombin detection by optical extinction LSPR. We also tested the LSPR sensor fabricated using gold bipyramid, which showed higher refractive index sensitivity than the gold nanorods, but the overall response of gold bipyramid sensor appears to be 25% less than that of the gold nanorod substrate, despite the approximately twofold higher refractive index sensitivity. XPS analysis showed that this is due to the low surface density of aptamers on the gold bipyramid compared with gold nanorods. The low surface density of the aptamers on the gold bipyramid surface may be due to the effect of shape of the nanostructure on the kinetics of aptamer monolayer formation. The small size of aptamers relative to other bioreceptors is the key to achieving high sensitivity by biosensors on the basis of LSPR, demonstrated here for protein binding. The generality of aptamer sensors for protein detection using gold nanorod and gold nanobipyramid substrates is anticipated to have a large impact in the important development of sensors toward biomarkers, environmental toxins, and warfare agents. Copyright © 2013 John Wiley & Sons, Ltd.     

A Localized Surface Plasmon Resonance Biosensor Based on Integrated Controllable Au2S/AuAgS-Coated Gold Nanorods Composite

In this work, we have demonstrated that the exquisite optical properties based on localized surface plasmon resonance (LSPR) of Au₂S/AuAgS-coated gold nanorods (Au₂S/AuAgS-coated GNRs) can be utilized to develop a simple and sensitive biosensor, and goat anti-human IgG can be detected by the human IgG probe as low as 0.2 nM. Moreover, we introduce an integrated LSPR biosensor constructed by integrating Au₂S/AuAgS-coated GNRs immobilized on glass slide and isolated Au₂S/AuAgS-coated GNRs in the form of liquid. The detection of target binding was performed via direct spectral changes induced by changes of refractive index in the vicinity of individual particles. The integrated LSPR optical biosensor is label-free, cost-effective, and easy to fabricate and requires only a visible/near-infrared spectrometer for detection purposes. Additionally, the investigation on the mutual influence of the two types of nanorods in the integrated LSPR biosensor was performed. The results of separate experiments indicate that the nanorods in the form of isolate or in integrated exhibit a similar behavior.     

Influence of a shape of gold nanoparticles on the dose enhancement in the wide range of gold mass concentration for high-energy X-ray beams from a medical linac

AimThis work is focused on the Monte Carlo microdosimetric calculations taking into account the influence of the AuNPs’ shape, size and mass concentration on the radiation dose enhancement for the high-energy 6 MV and 18 MV X-ray therapeutic beams from a medical linac.BackgroundDue to a high atomic number and the photoelectric effect, gold nanoparticles can significantly enhance doses of ionizing radiation. However, this enhancement depends upon several parameters, such as, inter alia, nanoparticles’ shape etc.MethodThe simulated system was composed of the therapeutic beam, a water phantom with the target volume (with and without AuNPs) located at the depth of the maximum dose, i.e. at 1.5 cm for the 6 MV beam and at 3.5 cm for the 18 MV one. In the study the GEANT4 code was used because it makes it possible to get a very short step of simulation which is required in case of simulating the radiation interactions with nanostructures.ResultsThe dependence between the dose increase and the mass concentration of gold was determined and described by a simple mathematical formula for three different shapes of gold nanoparticles — two nanorods of different sizes and a flat 2D structure. The dose increase with the saturation occurring with the increasing mass concentration of gold was observed.ConclusionsIt was found that relatively large cylindrical gold nanoparticles can limit the increase of the dose absorbed in the target volume much more than the large 2D gold nanostructure.     

Intracellular uptake,transport, and processing of gold nanostructures

Abstract

The emerging field of nanomedicine requires better understanding of the interface between nanotechnology and medicine. Better knowledge of the nano-bio interface will lead to better tools for diagnostic imaging and therapy. In this review, recent progress in understanding of how size, shape, and surface properties of nanoparticles (NPs) affect intracellular fate of NPs is discussed. Gold nanostructures are used as a model system in this regard since their physical and chemical properties can be easily manipulated. The NP-uptake is dependent on the physiochemical properties, and once in the cell, most of the NPs are trafficked via an endo-lysosomal path followed by a receptor-mediated endocytosis process at the cell membrane. Within the size range of 2–100 nm, Gold nanoparticles (GNPs) of diameter 50 nm demonstrate the highest uptake. Cellular uptake studies of gold nanorods (GNRs) show that there is a decrease in uptake as the aspect ratio of GNRs increases. Theoretical models support the size- and shape-dependent NP-uptake. The intracellular transport of targeted NPs is faster than untargeted NPs. The surface ligand and charge of NPs play a bigger role in their uptake, transport, and organelle distribution. Exocytosis of NPs is dependent on size and shape as well; however, the trend is different compared to endocytosis. GNPs are now being incorporated into polymer and lipid based NPs to build multifunctional devices. A multifunctional platform based on gold nanostructures, with multimodal imaging, targeting, and therapeutics; hold the possibility of promising directions in medical research.     

Nanodiamonds for bioapplications–specific targeting strategies

BackgroundNanodiamonds (NDs) provide a unique multitasking system for drug delivery and fluorescent imaging in biological environments. Owing to their quantum properties, NDs are expected to be employed as multifunctional probes in the future for the accurate visualization of biophysical parameters such as temperature and magnetic fields. However, the use of NDs for the selective targeting of the biomolecules of interest within a complicated biological system remains a challenge. One of the most promising solutions is the appropriate surface design of NDs based on organic chemistry and biochemistry. The engineered NDs have high biocompatibility and dispersibility in a biological environment and hence undergo cellular uptake through specific pathways.Scope of reviewThis review focuses on the selective targeting of NDs for biomedical and biophysical applications from the viewpoint of ND surface functionalizations and modifications. These pretreatments make possible the specific targeting of biomolecules of interest on or in a cell by NDs via a designed biochemical route.Major conclusionsThe surface of NDs is covalently or noncovalently modified with silica, polymers, or biomolecules to reshape them, control their size, and enhance the colloidal stability and biomolecular selectivity toward the biomolecules of interest. Electroporation, chemical treatment, injection, or endocytosis are the methods generally adopted to introduce NDs into living cells. The pathway, efficiency, and the cell viability depend on the selected method.General significanceIn the biomedical field, the surface modification facilitates specific delivery of a drug, leading to a higher therapeutic efficacy. In biophysical applications, the surface modification paves the way for the accurate measurement of physical parameters to gain a better understanding of various cell functions.     

Sensitive and Robust Colorimetric Sensing of Sulfide Anion by Plasmonic Nanosensors Based on Quick Crystal Growth

A highly sensitive and selective method for colorimetric sensing of sulfide anions in aqueous solutions is illustrated. The sensing mechanism is based on quick crystallization from Ag to Ag₂S in the presence of sulfide anions which alter the dielectric properties of the Au/Ag core/shell nanorods. The longitudinal surface plasmon resonance peak of the Au/Ag nanorods at about 686 nm undergoes a redshift and the color of the nanorod solution also changes from light green to purple. Sulfide ions at a concentration of 4.0 μM (1.3 ppb) can be detected visually and a sensitivity of 0.5 μM (167 ppt) is achieved by Vis–near-infrared spectrophotometry. Compared to other plasmonic sensors, our Au/Ag nanorod probe does not require surface modification while exhibiting high stability and robustness under different pH conditions. This simple and cost-effective sensing platform provides a rapid and convenient detection for sulfide anions at concentrations far below the hazardous limit in aqueous media.     

金纳米棒的表面修饰及其应用于肿瘤诊疗的研究进展

金纳米棒具有独特的光学性质、表面易修饰性、较低的生物毒性和良好的生物相容性,因而在成像、光热治疗和药物载带等方面具有极高的潜在应用价值.本文综述了典型的金纳米棒表面修饰方法及其在生物成像、光热治疗和药物治疗中的应用,重点阐述了通过金纳米棒同时实现肿瘤诊断和治疗相结合的研究进展.     

Active accumulation of gold nanorods in tumor in response to near-infrared laser irradiation

Gold nanorods, rod-shaped gold nanoparticles, have strong absorbance in the near-infrared region, and the absorbed light energy can be converted to heat, the so-called photothermal effect. The gold nanorods were coated with thermoresponsive polymers, which have different phase transition temperatures that were controlled by adding comonomers, N,N-dimethylacrylamide (DMAA) or acrylamide (AAm) to N-isopropylacrylamide (NIPAM). The phase transition temperatures of poly(NIPAM-DMAA) and poly(NIPAM-AAm)-coated gold nanorods were 38 and 41 °C, respectively, while polyNIPAM-coated gold nanorods showed phase transition at 34 °C. Irradiation of the coated gold nanorods using the near-infrared laser induced a decrease in their sizes due to a phase transition of the polymer layers. Poly(NIPAM-AAm)-coated gold nanorods stably circulated in the blood flow without a phase transition after intravenous injection. Irradiation of near-infrared light at a tumor after the injection resulted in the gold specifically accumulating in the tumor. This novel accumulation technique which combines a thermoresponsive polymer and the photothermal effect of the gold nanorods should be a powerful tool for targeted delivery in response to light irradiation.     

Gold Nanostar Synthesis with a Silver Seed Mediated Growth Method

The physical, chemical and optical properties of nano-scale colloids depend on their material composition, size and shape ^1-5. There is a great interest in using nano-colloids for photo-thermal ablation, drug delivery and many other biomedical applications ⁶. Gold is particularly used because of its low toxicity ^7-9. A property of metal nano-colloids is that they can have a strong surface plasmon resonance ¹⁰. The peak of the surface plasmon resonance mode depends on the structure and composition of the metal nano-colloids. Since the surface plasmon resonance mode is stimulated with light there is a need to have the peak absorbance in the near infrared where biological tissue transmissivity is maximal ^{11, 12}.We present a method to synthesize star shaped colloidal gold, also known as star shaped nanoparticles ^13-15 or nanostars ¹⁶. This method is based on a solution containing silver seeds that are used as the nucleating agent for anisotropic growth of gold colloids ^17-22. Scanning electron microscopy (SEM) analysis of the resulting gold colloid showed that 70 % of the nanostructures were nanostars. The other 30 % of the particles were amorphous clusters of decahedra and rhomboids. The absorbance peak of the nanostars was detected to be in the near infrared (840 nm). Thus, our method produces gold nanostars suitable for biomedical applications, particularly for photo-thermal ablation.     

Gold nanorods targeted to delta opioid receptor: plasmon-resonant contrast and photothermal agents

Molecularly targeted gold nanorods were investigated for applications in both diagnostic imaging and disease treatment with cellular resolution. The nanorods were tested in two genetically engineered cell lines derived from the human colon carcinoma HCT-116, a model for studying ligand-receptor interactions. One of these lines was modified to express delta opioid receptor (deltaOR) and green fluorescent protein, whereas the other was receptor free and expressed a red fluorescent protein, to serve as the control. Deltorphin, a high-affinity ligand for deltaOR, was stably attached to the gold nanorods through a thiol-terminated linker. In a mixed population of cells, we demonstrated selective imaging and destruction of receptor-expressing cells while sparing those cells that did not express the receptor. The molecularly targeted nanorods can be used as an in vitro ligand-binding and cytotoxic treatment assay platform and could potentially be applied in vivo for diagnostic and therapeutic purposes with endoscopic technology.     

Designable nanoplasmonic biomarkers for direct microscopy cytopathology diagnostics

Direct microscopy interpretation of fine‐needle biopsy cytological samples is routinely used by practicing cytopathologists. Adding possibility to identify selective and multiplexed biomarkers on the same samples and with the same microscopy technique can greatly improve diagnostic accuracy. In this article, we propose to use biomarkers based on designable plasmonic nanoparticles (NPs) with unique optical properties and excellent chemical stability that can satisfy the above‐mentioned requirements. By finely controlling the size and composition of gold‐silver alloy NPs and gold nanorods, the NPs plasmonic resonance properties, such as scattering efficiency and resonance peak spectral position, are adjusted in order to provide reliable identification and chromatic differentiation by conventional direct microscopy. Efficient darkfield NPs imaging is performed by using a novel circular side illumination adaptor that can be easily integrated into any microscopy setup while preserving standard cytopathology visualization method. The efficiency of the proposed technology for fast visual detection and differentiation of three spectrally distinct NP‐markers is demonstrated in different working media, thus confirming the potential application in conventional cytology preparations. It is worth emphasizing that the presented technology does not interfere with standard visualization with immunohistochemical staining, but should rather be considered as a second imaging modality to confirm the diagnostics.      

Functionalized Plasmonic Anisotropic Nanocrystals for Multimodal Imaging of Cancer Cells

Nanoparticles internalized by cells are valuable probes for bioimaging. In particular, nanoparticles can be detected in “biological transmission window,” i.e., near infrared region. Here, we report a preparation of biotargeting diethylthiatricarbocyanine iodide (DTTC)-functionalized gold nanorods, utilized for detection of malignant cells. These biotargeting DTTC-functionalized gold nanorods are efficiently internalized into cultured cells and can serve as probes for surface-enhanced Raman scattering (SERS) and dark-field imaging. The robust SERS signal from malignant cells has clearly demonstrated a signature peak of DTTC in the presence of our formulation. A short acquisition time, we used in this experiment, is able to exclude bulk of Raman signal from natural cellular constituents. This signature peak will be a key of identifying cancer due to cancer-specific property of biotargeted molecule. The results are leading to promising real-time cancer detection. In addition, these multimodal probes demonstrated low toxicity in cell viability studies which enables a broad range of multiplex imaging applications.     

Enhanced photoinactivation of Staphylococcus aureus with nanocomposites containing plasmonic particles and hematoporphyrin

We fabricated composite nanoparticles consisting of a plasmonic core (gold nanorods or gold–silver nanocages) and a hematoporphyrin‐doped silica shell. The dual photodynamic and photothermal activities of such nanoparticles against Staphylococcus aureus 209 P were studied and compared with the activities of reference solutions (hematoporphyrin or silica‐coated plasmonic nanoparticles). Bacteria were incubated with nanocomposites or with the reference solutions for 15 min, which was followed by CW light irradiation with a few exposures of 5 to 30 min. To stimulate the photodynamic and photothermal activities of the nanocomposites, we used LEDs (405 and 625 nm) and a NIR laser (808 nm), respectively. We observed enhanced inactivation of S. aureus 209 P by nanocomposites in comparison with the reference solutions. By using fluorescence microscopy and spectroscopy, we explain the enhanced antimicrobial effect of hematoporphyrin‐doped nanocomposites by their selective accumulation in the vicinity of the bacteria. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Study of gold nanoparticles for mammography diagnostic and radiotherapy improvements

AimA study on the possibility to use gold nanoparticles in mammography, both for a better image diagnostics and radiotherapy, is presented and discussed. We evaluate quantitatively the increment of dose released to the tumor enriched with Au-NPs with respect to the near healthy tissues, finding that for X-rays the increase can reach two orders of greater intensity.BackgroundGold nanoparticles continue to be investigated for their potential to improve existing therapies and to develop novel therapies. They are simple to obtain, can be functionalized with different chemical approaches, are stable, non-toxic, non-immunogenic and have high permeability and retention effects in the tumor cells. The possibility to use these for breast calcified tumors to be better treated by radiotherapy is presented as a possible method to destroy the tumor.Materials and methodsThe nanoparticles can be generated in water using the top-down method, should have a size of the order of 10–20 nm and be treated to avoid their coalescence. Under diagnostic X-ray monitoring, the solution containing nanoparticles can be injected locally inside the tumor site avoiding injection in healthy tissues. The concentrations that can be used should be of the order of 10 mg/ml or higher.ResultsAn enhancement of the computerized tomography diagnostics using 80–150 keV energy is expected, due to the higher mass X-ray coefficient attenuation with respect to other contrast media. Due to the increment of the effective atomic number of the biological tissue containing the gold nanoparticles, also an improvement of the radiotherapy effect using about 30 keV X-ray energy is expected, due to the higher photoelectric cross sections involved.ConclusionsThe study carried out represents a feasibility proposal for the use of Au-nanoparticles for mammographic molecular imaging aimed at radiotherapy of tumor nodules but no clinical results are presented.