Irradiation Of Gold Nanoparticles Research Articles

Both experimental and molecular dynamics approaches highlight the central role of interfacial water for radical production by irradiated gold nanoparticles

Nanoparticles devoted to improve radiotherapy treatments are an efficient tool if they can induce the formation of deleterious species in the tumor. Their interaction with radiation is responsible for radical production but in spite of the numerous studies mostly with cells, no consensus has been reached about radical formation mechanism. In order to gain knowledge in the physico-chemical step of this phenomenon, we applied a very sensitive test to quantify hydroxyl radicals and electrons produced when gold atoms, organized as nanoparticles or as a salt in solution, are irradiated by keV and MeV photons (x- and γ- rays). The crucial role of interfacial water is suggested to explain the high quantity of radicals measured for nanoparticles. These experimental data were supplemented by classical molecular dynamics simulations, revealing a specific organization of the water hydrogen bonding network at the nanoparticle surface which could be a key component in the mechanism of radical production by irradiated colloidal suspensions.

Role of lattice defects on the magnetism of gold nanoparticles irradiated with neutrons

The origin of the unexpected magnetic properties of nanoparticles made of gold, silver, or other diamagnetic metals remains obscure despite a large body of experimental and theoretical studies. Whereas many studies have endeavoured at finding correlations between magnetism and nanoparticle size or ligand coating, none so far has attempted at investigating the role of core crystallinity. We have irradiated gold nanoparticles with energetic neutrons or protons with the aim of nucleating lattice defects in the crystalline cores. Comparison of the magnetic behaviours before and after irradiation demonstrates clearly that the presence of defects in the crystalline lattice of the nanoparticles cores contributes efficiently to their magnetism.

Direct laser writing of 3D microstructures at solid-liquid interfaces by plasmonic bubbles

Plasmonic microbubbles produced by laser irradiated gold nanoparticles (GNPs) in various liquids have emerged in numerous innovative applications. The nucleation of these bubbles inherently involves rich phenomena. In this paper, we systematically investigate the physicochemical hydrodynamics of plasmonic bubbles upon irradiation of a continuous wave (CW) laser on a GNP decorated sample surface in ferric nitrate solution. Surprisingly, we observe the direct formation of well-defined micro-domes on the sample surface. This reveals that the nucleation of a plasmonic bubble is associated with the solvothermal decomposition of ferric nitrate in the solution. The plasmonic bubble acts as a template for the deposition of iron oxide nanoparticles. It first forms a rim, then a micro-shell, which eventually becomes a solid micro-dome. Experimental results show that the micro-dome radius Rd exhibits an obvious Rd ∝ t1/3 dependence on time t, which can be well interpreted theoretically. Our findings reveal the rich phenomena associated with plasmonic bubble nucleation in a thermally decomposable solution, paving the way for a plasmonic bubble based approach to fabricating three dimensional microstructures using an ordinary CW laser.

Mechanisms of Nanoscale Radiation Enhancement by Metal Nanoparticles: Role of Low Energy Electrons.

Metal nanoparticles are considered as highly promising radiosensitizers in cancer radiotherapy. Understanding their radiosensitization mechanisms is critical for future clinical applications. This review is focused on the initial energy deposition by short-range Auger electrons; when high energy radiation is absorbed by gold nanoparticles (GNPs) located near vital biomolecules; such as DNA. Auger electrons and the subsequent production of secondary low energy electrons (LEEs) are responsible for most the ensuing chemical damage near such molecules. We highlight recent progress on DNA damage induced by the LEEs produced abundantly within about 100 nanometers from irradiated GNPs; and by those emitted by high energy electrons and X-rays incident on metal surfaces under differing atmospheric environments. LEEs strongly react within cells; mainly via bound breaking processes due to transient anion formation and dissociative electron attachment. The enhancement of damages induced in plasmid DNA by LEEs; with or without the binding of chemotherapeutic drugs; are explained by the fundamental mechanisms of LEE interactions with simple molecules and specific sites on nucleotides. We address the major challenge of metal nanoparticle and GNP radiosensitization; i.e., to deliver the maximum local dose of radiation to the most sensitive target of cancer cells (i.e., DNA). To achieve this goal the emitted electrons from the absorbed high energy radiation must be short range, and produce a large local density of LEEs, and the initial radiation must have the highest possible absorption coefficient compared to that of soft tissue (e.g., 20-80 keV X-rays).

Using irradiated gold nanoparticles to treat cancer

Using irradiated gold nanoparticles to treat cancer

Incorporation of Low Concentrations of Gold Nanoparticles: Complex Effects on Radiation Response and Fate of Cancer Cells.

(1) Background: In oncology research, a long-standing discussion exists about pros and cons of metal nanoparticle-enhanced radiotherapy and real mechanisms behind the tumor cell response to irradiation (IR) in presence of gold nanoparticles (GNPs). A better understanding of this response is, however, necessary to develop more efficient and safety nanoparticle (NP) types designed to disturb specific processes in tumor cells. (2) Aims and Methods: We combined 3D confocal microscopy and super-resolution single molecule localization microscopy (SMLM) to analyze, at the multiscale, the early and late effects of 10 nm-GNPs on DNA double strand break (DSB) induction and repair in tumor cells exposed to different doses of photonic low-LET (linear energy transfer) radiation. The results were correlated to different aspects of short and long-term cell viability. SkBr3 breast cancer cells (selected for the highest incidence of this cancer type among all cancers in women, and because most breast tumors are treated with IR) were incubated with low concentrations of GNPs and irradiated with 60Co γ-rays or 6 MV X-rays. In numerous post-irradiation (PI) times, ranging from 0.5 to 24 h PI, the cells were spatially (3D) fixed and labeled with specific antibodies against γH2AX, 53BP1 and H3K9me3. The extent of DSB induction, multi-parametric micro- and nano-morphology of γH2AX and 53BP1 repair foci, DSB repair kinetics, persistence of unrepaired DSBs, nanoscale clustering of γH2AX and nanoscale (hetero)chromatin re-organization were measured by means of the mentioned microscopy techniques in dependence of radiation dose and GNP concentration. (3) Results: The number of γH2AX/53BP1 signals increased after IR and an additional increase was observed in GNP-treated (GNP(+)) cells compared to untreated controls. However, this phenomenon reflected slight expansion of the G2-phase cell subpopulation in irradiated GNP(+) specimens instead of enhanced DNA damage induction by GNPs. This statement is further supported by some micro- and nano-morphological parameters of γH2AX/53BP1 foci, which slightly differed for cells irradiated in absence or presence of GNPs. At the nanoscale, Ripley’s distance frequency analysis of SMLM signal coordinate matrices also revealed relaxation of heterochromatin (H3K9me3) clusters upon IR. These changes were more prominent in presence of GNPs. The slight expansion of radiosensitive G2 cells correlated with mostly insignificant but systematic decrease in post-irradiation survival of GNP(+) cells. Interestingly, low GNP concentrations accelerated DSB repair kinetics; however, the numbers of persistent γH2AX/53BP1 repair foci were slightly increased in GNP(+) cells. (4) Conclusions: Low concentrations of 10-nm GNPs enhanced the G2/M cell cycle arrest and the proportion of radiosensitive G2 cells, but not the extent of DNA damage induction. GNPs also accelerated DSB repair kinetics and slightly increased presence of unrepaired γH2AX/53BP1 foci at 24 h PI. GNP-mediated cell effects correlated with slight radiosensitization of GNP(+) specimens, significant only for the highest radiation dose tested (4 Gy).

Tethered Bilayer Lipid Membranes to Monitor Heat Transfer between Gold Nanoparticles and Lipid Membranes.

Here we report a protocol to investigate the heat transfer between irradiated gold nanoparticles (GNPs) and bilayer lipid membranes by electrochemistry using tethered bilayer lipid membranes (tBLMs) assembled on gold electrodes. Irradiated modified GNPs, such as streptavidin-conjugated GNPs, are embedded in tBLMs containing target molecules, such as biotin. By using this approach, the heat transfer processes between irradiated GNPs and model bilayer lipid membrane with entities of interest are mediated by a horizontally focused laser beam. The thermal predictive computational model is used to confirm the electrochemically induced conductance changes in the tBLMs. Under the specific conditions used, detecting heat pulses required specific attachment of the gold nanoparticles to the membrane surface, while unbound gold nanoparticles failed to elicit a measurable response. This technique serves as a powerful detection biosensor which can be directly utilized for the design and development of strategies for thermal therapies that permits optimization of the laser parameters, particle size, particle coatings and composition.

Decomposition of halogenated nucleobases by surface plasmon resonance excitation of gold nanoparticles

Halogenated uracil derivatives are of great interest in modern cancer therapy, either as chemotherapeutics or radiosensitisers depending on their halogen atom. This work applies UV-Vis spectroscopy to study the radiation damage of uracil, 5-bromouracil and 5-fluorouracil dissolved in water in the presence of gold nanoparticles upon irradiation with an Nd:YAG ns-pulsed laser operating at 532 nm at different fluences. Gold nanoparticles absorb light efficiently by their surface plasmon resonance and can significantly damage DNA in their vicinity by an increase of temperature and the generation of reactive secondary species, notably radical fragments and low energy electrons. A recent study using the same experimental approach characterized the efficient laser-induced decomposition of the pyrimidine ring structure of 5-bromouracil mediated by the surface plasmon resonance of gold nanoparticles. The present results show that the presence of irradiated gold nanoparticles decomposes the ring structure of uracil and its halogenated derivatives with similar efficiency. In addition to the fragmentation of the pyrimidine ring, for 5-bromouracil the cleavage of the carbon-halogen bond could be observed, whereas for 5-fluorouracil this reaction channel was inhibited. Locally-released halogen atoms can react with molecular groups within DNA, hence this result indicates a specific mechanism by which doping with 5-bromouracil can enhance DNA damage in the proximity of laser irradiated gold nanoparticles.Graphical abstract

Laser-Assisted Delivery of Molecules in Fungal Cells.

Fungal infections are becoming a global health problem. A major limiting factor for the development of antifungals is the high impermeability of the rigid and thick fungal cell wall. Compared to mammalian cells, fungal cells are more resilient to perforation due to the presence of this carbohydrate armor. While a few methods have been reported to penetrate the fungal cell wall, such as electroporation, biolistics, glass beads, and the use of monovalent cations, such methods are generally time-consuming, compromise cell viability, and often lead to low permeation rates. In addition, their use remains limited to in vitro applications due to the collateral damage that these techniques could cause to healthy living tissues. Presented in this study is a delivery approach based on the generation of transient breaks, or pores, in the cell wall. Breaks are generated by cavitation and shock waves resulting from the irradiation of gold nanoparticles with a femtosecond infrared laser. Such an approach enabled the delivery of membrane impermeable molecules (i.e., calcein and plasmid DNA) into Saccharomyces cerevisiae, a fungal model organism. This method is expected to exhibit high biocompatibility and holds potential for clinical applications for the treatment of fungal infections given that neither the laser irradiation nor the nanoparticles have been found to damage cells. Mechanistical aspects of photoporation, such as the proximity needed between the nanoparticle and the cell membrane for these processes to take place, are also discussed. Hence, the laser-assisted drug delivery approach described here is suitable for further preclinical evaluation in oral, vaginal, and skin mycoses where current treatments are insufficient due to host-related adverse reactions, poor fungal cell penetration, or risk of developing antifungal resistance.

Real-time monitoring of heat transfer between gold nanoparticles and tethered bilayer lipid membranes

Plasmon resonance frequency irradiated gold nanoparticles (GNPs) have gained interest as a laser-targeted treatment for infections, tumors and for the controlled release of drugs in situ. Questions still remain, however, as to the efficiency of heat delivery within biological tissues and how this can be reliably determined. Here, we demonstrate how a nanomaterial-electrode interface that mimics cell membranes can detect the localized heat transfer characteristics arising from plasmon resonance frequency-matched laser excitation of GNPs. We demonstrate that the lipid bilayer membrane can be affected by conjugated GNP induced hyperthermia when irradiated with a laser power output as low as 135 nW/μm2. This is four orders of magnitude lower power than previously reported. By restricting the lateral movement of the lipids in the bilayer membrane, it was shown that the change in membrane conductance as a result of the heat transfer was due to the creation of transient lipidic toroidal pores within the membrane. We further demonstrate that the heat transfer from the GNPs alters diffusion rates of monomers of the gramicidin-A peptide within the lipid leaflets. This work highlights how targeted low laser power GNP hyperthermia treatments, in vivo, could play a dual role of interfering with both cell membrane morphology and dynamics, along with membrane protein function.

Kinetics of molecular decomposition under irradiation of gold nanoparticles with nanosecond laser pulses-A 5-Bromouracil case study.

Laser illuminated gold nanoparticles (AuNPs) efficiently absorb light and heat up the surrounding medium, leading to versatile applications ranging from plasmonic catalysis to cancer photothermal therapy. Therefore, an in-depth understanding of the thermal, optical, and electron induced reaction pathways is required. Here, the electrophilic DNA nucleobase analog 5-Bromouracil (BrU) has been used as a model compound to study its decomposition in the vicinity of AuNPs illuminated with intense ns laser pulses under various conditions. The plasmonic response of the AuNPs and the concentration of BrU and resulting photoproducts have been tracked by ultraviolet and visible (UV-Vis) spectroscopy as a function of the irradiation time. A kinetic model has been developed to determine the reaction rates of two parallel fragmentation pathways of BrU, and their dependency on laser fluence and adsorption on the AuNP have been evaluated. In addition, the size and the electric field enhancement of the decomposed AuNPs have been determined by atomic force microscopy and finite domain time difference calculations, respectively. A minor influence of the direct photoreaction and a strong effect of the heating of the AuNPs have been revealed. However, due to the size reduction of the irradiated AuNPs, a trade-off between laser fluence and plasmonic response of the AuNPs has been observed. Hence, the decomposition of the AuNPs might be limiting the achievable temperatures under irradiation with several laser pulses. These findings need to be considered for an efficient design of catalytic plasmonic systems.

Quantification of hydroxyl radicals and solvated electrons produced by irradiated gold nanoparticles suggests a crucial role of interfacial water

The potential benefit of gold nanoparticles (GNP) to radiotherapy has been demonstrated in a range of cell lines and radiation sources as well as in rodent models, sometimes with contradictory results. Few experimental studies have explored the involved deleterious species, hydroxyl radical being so far the most cited, whereas theoretical studies have usually focused on secondary electrons emitted from GNP, making comparison between these two approaches difficult. Here we focus on the physico-chemical step (i.e. radical production) and report the first experimental determination of both hydroxyl radicals and solvated electrons yields of formation in the presence of GNP. We also compare these yields between X- and γ-rays under different atmospheres. Our main finding is a massive and equivalent production of both species under X- and more surprisingly γ-rays. For concentration as low as 1 nM (0.02% wt of gold), both radiations lead to 3 to 4 times more radicals than water radiolysis without GNP. This is in contradiction with a physical prediction of dose enhancement. Supported by our whole set of experiments the key role of water molecules at the nanoparticle interface in the radical production emerges. This leads us to propose the paramount importance of the physico-chemical step compared to the physical one. Classical approaches based on energy-absorption coefficients and electron ejections should therefore be revisited.

The Effective Killing Percentages of Hela Cells By Gold Nanoparticles and IR Irradiation

Cancer photothermal therapy (PTT) depends on the size, and shape of nanoparticles, consequently, on the surface plasmon resonance (SPR) peaks of the gold nanoparticles (GNPs) synthesized by pulsed laser ablation (PLA) method in Dulbecco’s Modified Eagle Medium (DMED), found to be located between (549-580) nm. The size of GNPs measured the calculation of SPR spectra, dynamic light scattering (DLS) methods and analysis of the transmission electron microscope (TEM) images were found to be ranged between (59-116) nm. The concentration of GNPs in prepared colloidal solution found ranged between (8-16) ppm. Irradiation of GNPs which incubated with Hela cells for 24 h by R light for (15,30, and 45) minutes, enhanced the killing percentage especially for GNPs diameters (50- 70) nm.

Local Enhancement of Lipid Membrane Permeability Induced by Irradiated Gold Nanoparticles.

Photothermal therapies are based on the optical excitation of plasmonic nanoparticles in the biological environment. The effects of the irradiation on the biological medium depend critically on the heat transfer process at the nanoparticle interface, on the temperature reached by the tissues, as well as on the spatial extent of temperature gradients. Unfortunately, both the temperature and its biological effects are difficult to be probed experimentally at the molecular scale. Here, we approach this problem using nonequilibrium molecular dynamics simulations. We focus on photoporation, a photothermal application based on the irradiation of gold nanoparticles by single, short-duration laser pulses. The nanoparticles, stably bound to cell membranes, convert the radiation into heat, inducing transient changes of membrane permeability. We make a quantitative prediction of the temperature gradient around the nanoparticle upon irradiation by typical experimental laser fluences. Water permeability is locally enhanced around the nanoparticle, in an annular region that extends only a few nanometers from the nanoparticle interface. We correlate the local enhancement of permeability at the nanoparticle-lipid interface to the temperature inhomogeneities of the membrane and to the consequent availability of free volume pockets within the membrane core.

Temperature dynamics of laser irradiated gold nanoparticles embedded in a polymer matrix

In this work the temperature evolution, in time and space, in two systems that consist of a single gold nanoparticle and an ensemble of gold nanoparticles, both embedded in a polystyrene sulfonic acid matrix, is numerically modeled. The heat accumulated by the gold nanoparticles is estimated considering the system irradiation with a nanosecond laser at 532nm. The distribution of the temperature in time and space is calculated by solving the heat diffusion equations with appropriate initial and boundary conditions. The rise of nanoparticle size determined the temperature increase of the gold nanoparticle and implicitly of the entire system but also the increase of the necessary time for reaching the thermal equilibrium of the system related to the surrounding polymer volume. The temperature evolution and the dynamics of the system towards reaching the thermal equilibrium are influenced by the gold nanoparticles distribution in the polymer matrix.

Impact of fluorescence emission from gold atoms on surrounding biological tissue—implications for nanoparticle radio-enhancement

The addition of gold nanoparticles within target tissue (i.e. a tumour) to enhance the delivered radiation dose is a well studied radiotherapy treatment strategy, despite not yet having been translated into standard clinical practice. While several studies have used Monte Carlo simulations to investigate radiation dose enhancement by Auger electrons emitted from irradiated gold nanoparticles, none have yet considered the effects due to escaping fluorescence photons.Geant4 was used to simulate a water phantom containing 10 mg ml−1 uniformly dispersed gold (1% by mass) at 5 cm depth. Incident monoenergetic photons with energies either side of the gold K-edge at 73 keV and 139.5 keV were chosen to give the same attenuation contrast against water, where water is used as a surrogate for biological tissue.For 73 keV incident photons, adding 1% gold into the water phantom enhances the energy deposited in the phantom by a factor of ≈1.9 while 139.5 keV incident photons give a lower enhancement ratio of ≈1.5. This difference in enhancement ratio, despite the equivalent attenuation ratios, can be attributed to energy carried from the target into the surrounding volume by fluorescence photons for the higher incident photon energy. The energy de-localisation is maximal just above the K-edge with 36% of the initial energy deposit in the phantom lost to escaping fluorescence photons.Conversely we find that the absorption of more photons by gold in the phantom reduces the number of scattered photons and hence energy deposited in the surrounding volume by up to 6% for incident photons below the K-edge. For incident photons above the K-edge this is somewhat offset by fluorescence.Our results give new insight into the previously unstudied centimetre scale energy deposition outside a target, which will be valuable for the future development of treatment plans using gold nanoparticles. From these results, we can conclude that gold nanoparticles delivered to a target tumour are capable of increasing dose to the tumour whilst simultaneously decreasing scatter dose to surrounding healthy tissue.

Modulation of cardiomyocyte activity using pulsed laser irradiated gold nanoparticles.

Can photothermal gold nanoparticle mediated laser manipulation be applied to induce cardiac contraction? Based on our previous work, we present a novel concept of cell stimulation. A 532 nm picosecond laser was employed to heat gold nanoparticles on cardiomyocytes. This leads to calcium oscillations in the HL-1 cardiomyocyte cell line. As calcium is connected to the contractility, we aimed to alter the contraction rate of native and stem cell derived cardiomyocytes. A contraction rate increase was particularly observed in calcium containing buffer with neonatal rat cardiomyocytes. Consequently, the study provides conceptual ideas for a light based, nanoparticle mediated stimulation system.

O46. X-ray, [formula omitted] and neutron irradiated spherical gold nanoparticles in human breast epithelium and human skin keratinocyte cells

Introduction Auger electron-emitting radiopharmaceuticals are attractive for nano-irradiation therapy, given that DNA of malignant cells is selectively targeted. The limited penetration of kV X-rays, in comparison to megavoltage (MV), is a challenge of radiotherapy and gold nanoparticles (AuNPs) have been identified as effective radiosensitisers following bombardment with low energy (e.g. 200–500 keV) radiation. Materials and methods AuNPs were synthesised via the ‘green nanotechnology’ method using cinnamon (Cinn-), red-speckled beans (RSB-) and soybeans (SB-) as phytochemical reservoirs for the reduction and stabilisation of gold salts to AuNPs. Skin (HaCaT), breast (MCF10A), and malignant breast (MCF7) cell lines were treated with each AuNP type, and radiated with either 2 Gy 60 Co γ - or X-rays, or 1 Gy p(66)/Be(49) neutrons. The cytokinesis-block micronucleus assay was used to determine the presence of micronuclei (MNi) within binucleated cells. Results An overall increase in MNi numbers were recorded for non-malignant HaCaT and MCF10A cells treated with AuNPs and exposed to X-ray radiation, whilst 60 Co γ -radiation caused less MNi. However, AuNPs served as radioprotective devices within the neoplastic MCF7 cell line wherein MNi numbers were much less after incubation with AuNP types and X-ray exposure. Furthermore, the RSBGA-AuNP seemed to have the greatest effect on MNi occurrence: the nanoparticle caused a sensitisation effect in HaCaT and MCF10A cells to γ - and neutron radiation, whilst serving as a radioprotector against X-ray exposure. However, for the cancerous MCF7 cells, RSBGA-AuNPs caused radioprotection against γ -radiation, whilst sensitising the cells to X-ray and neutron radiation after 24h incubation with AuNPs. Conclusion Several explanations were provided for the above occurrences, including: the size of the AuNPs, the failure of the AuNPs to penetrate the nuclear membrane, the formation of possible autophagosomal and lysosomal bodies sequestering the AuNPs, the effect AuNPs have on the cell cycle, and the radical scavenging capabilities of the phytochemical-coated AuNPs.

Reversible control of current across lipid membranes by local heating.

Lipid membranes are almost impermeable for charged molecules and ions that can pass the membrane barrier only with the help of specialized transport proteins. Here, we report how temperature manipulation at the nanoscale can be employed to reversibly control the electrical resistance and the amount of current that flows through a bilayer membrane with pA resolution. For this experiment, heating is achieved by irradiating gold nanoparticles that are attached to the bilayer membrane with laser light at their plasmon resonance frequency. We found that controlling the temperature on the nanoscale renders it possible to reproducibly regulate the current across a phospholipid membrane and the membrane of living cells in absence of any ion channels.

A Simple Model to Quantify Radiolytic Production following Electron Emission from Heavy-Atom Nanoparticles Irradiated in Liquid Suspensions.

We present a simple model for a component of the radiolytic production of any chemical species due to electron emission from irradiated nanoparticles (NPs) in a liquid environment, provided the expression for the G value for product formation is known and is reasonably well characterized by a linear dependence on beam energy. This model takes nanoparticle size, composition, density and a number of other readily available parameters (such as X-ray and electron attenuation data) as inputs and therefore allows for the ready determination of this contribution. Several approximations are used, thus this model provides an upper limit to the yield of chemical species due to electron emission, rather than a distinct value, and this upper limit is compared with experimental results. After the general model is developed we provide details of its application to the generation of HO• through irradiation of gold nanoparticles (AuNPs), a potentially important process in nanoparticle-based enhancement of radiotherapy. This model has been constructed with the intention of making it accessible to other researchers who wish to estimate chemical yields through this process, and is shown to be applicable to NPs of single elements and mixtures. The model can be applied without the need to develop additional skills (such as using a Monte Carlo toolkit), providing a fast and straightforward method of estimating chemical yields. A simple framework for determining the HO• yield for different NP sizes at constant NP concentration and initial photon energy is also presented.