Photoluminescent Gold Nanoclusters Research Articles

Magnetic Nanoparticles Decorated with Gold Nanoclusters–Applications in Cancer Theranostics

AbstractNanomedicine presents exciting new opportunities for the detection and treatment of cancer. Current cancer imaging methods and treatment approaches in clinics frequently fall short of entirely curing cancer and can have severe side effects. Theranostic nanoparticles, however, have the potential to revolutionize effective cancer treatment and early cancer detection. The objective of this study is to show how magnetic iron oxide nanoparticles and photoluminescent gold nanoclusters (MN‐AuNCs) may be combined effectively to produce bimodal imaging nanoparticles that possess magnetic and optical properties and can be used for both magnetic resonance imaging and optical biopsy. These findings demonstrate that MN‐AuNCs, when exposed to visible light, also have the capability to produce singlet oxygen, which is necessary for photodynamic therapy of cancer. In addition, it shows that they are non‐toxic, accumulate inside the cells, and cause cell death during exposure to visible light. The creation of these MN‐AuNCs offers a novel remedy for the current shortcomings in cancer diagnosis and treatment. Since they have both therapeutic and imaging capabilities, MN‐AuNCs have the potential to improve patient outcomes while lowering the risk of negative side effects.

Photoluminescent gold nanoclusters as two-photon excited ratiometric pH sensor and photoactivated peroxidase.

Atwo-photon excited ratiometric fluorescent pH sensor is reportedby combining L-cysteine-protected AuNCs (Cys@AuNCs) with fluorescein isothiocyanate (FITC). Cys@AuNCs were synthesized through a one-step self-reduction route and showed pH-responsive photoluminescence at 650 nm. Benefiting from the opposite pH response of Cys@AuNCs and FITC, the fluorescence ratio (F515 nm/F650 nm) of FITC&Cys@AuNCs provided a large dynamic range of 200-fold for pH measurement in the response interval of pH 5.0-8.0. Based on the excellent two-photon absorption coefficient of Cys@AuNCs, the sensor was expected to achieve sensitive quantitation of pH in living cells under two-photon excitation. In addition, colorimetric biosensing based on enzyme-like metal nanoclusters has attracted wide attention due to their low-cost, simplicity, and practicality. It is crucial to develop high catalytic activity nanozyme from the viewpoint of practical application. The synthesized Cys@AuNCs exhibited excellent photoactivated peroxidase-like activity with high substrate affinity and catalytic reaction rate, promising for rapid colorimetric biosensing of field analysis and the control of catalytic reactions by photostimulation.

Intracellular accumulation and immunological response of NIR-II polymeric nanoparticles

Polymeric nanoparticles (NPs) are extremely promising for theranostic applications. However, their interest depends largely on their interactions with immune system, including the capacity to activate inflammation after their capture by macrophages. In the present study, we generated monodisperse poly(ethyl methacrylate) (PEMA) NPs loaded with hydrophobic photoluminescent gold nanoclusters (Au NCs) emitting in the NIR-II optical windows and studied their interaction in vitro with J774.1A macrophages. PEMA NPs showed an efficient time and dose dependent cellular uptake with up to 70 % of macrophages labelled in 24 h without detectable cell death. Interestingly, PEMA and Au-PEMA NPs induced an anti-inflammatory response and a strong down-regulation of nitric oxide level on lipopolysacharides (LPS) activated macrophages, but without influence on the levels of reactive oxygen species (ROS). These polymeric NPs may thus present a potential interest for the treatment of inflammatory diseases.

Ligand evolution of luminescent gold nanoclusters: from amino acids to proteins

<p indent="0mm">Gold nanoclusters are known as emerging ultra-small-sized luminescent nanomaterials with the characteristics of strong photobleaching resistance, large Stokes shifts, good biocompatibility and low toxicity. Up to now, the development of emissive gold nanoclusters has experienced several stages, which are closely related to the study of ligands. Based on the evolution of ligands, this review focuses on how ligands from amino acids, peptides to proteins are used to synthesize photoluminescent gold nanoclusters and to fabricate biosensors. The content of this review includes synthesis methods, luminescence mechanism and stimuli-responsive properties of gold nanoclusters. The effects of different ligands on gold nanoclusters are discussed separately, and the current challenges and the future development direction in the field of gold nanoclusters are proposed.

Novel paper-based sensing platform using photoluminescent gold nanoclusters for easy, sensitive and selective naked-eye detection of Cu2+

Herein, we developed a novel, cheap, fast and simple portable sensing platform based on the photoluminescence (PL) quenching effect of paper-incorporated bovine serum albumin protein stabilized gold nanoclusters (BSA-AuNCs) when interacting with Cu ions (Cu2+) from real water samples. First, we demonstrated the sensibility and specificity of the BSA-AuNCs-based sensor for the detection of Cu2+ in solution via PL quenching effect, using a portable fluorescence spectrometer, under 502 nm LED excitation. The limit of detection (LOD) was found to be as low as 0.83 µM. For improved portability and accessibility, the sensing performance of BSA-AuNCs was successfully combined with the unique properties of Whatman paper substrates in order to develop a portable and ready-to-use sensor for the detection of Cu2+ from real water samples. The obtained BSA-AuNCs incorporated paper-based sensing substrate was successfully used for naked-eye detection of Cu2+ levels from water, under UV light, based on the visual detection of PL quenching. We obtained a LOD of 5 µM which was confirmed even for 14 days aged paper sensing substrates. The as-prepared BSA-AuNCs-paper-based sensor was validated for the detection of Cu2+ in different real water samples through the visual examination of the PL quenching on the paper substrates under UV light illumination and relevantly dangerous levels for humans or subaquatic organisms were successfully identified. The newly prepared BSA-AuNCs-incorporated paper-based sensing platform is easy-to-use and presents great promise in the fast, selective, qualitative and semi-quantitative naked-eye detection of Cu2+ in real water samples.

Excited-State Dynamics of Photoluminescent Gold Nanoclusters and Their Assemblies with Quantum Dot Donors

Gold nanoclusters (AuNCs) are a recently developed class of photoluminescent nanomaterial with potential for detection and imaging applications in both chemistry and biology. The AuNC small size (Au104NC) in combination with their long-lived, near-infrared (NIR) emission suggests that they could be applied as a biological label directly and also as a potential acceptor for energy transfer-based biosensing. Previous studies have shown that functionalized AuNCs can act as energy-transfer acceptors; however, the underlying mechanism appears to be complex and does not necessarily follow a classical Förster process with a (1/R)6 distance dependence. Here, we report a femtosecond and nanosecond time-resolved spectroscopy study to examine the energy dissipation and transfer processes of photoluminescent AuNC acceptors displaying different functionalized end groups and coupled with 625 nm emitting semiconductor quantum dot (QD) donors. Examination of AuNCs alone on the femtosecond timescale show coherent vibrational oscillations within the first 15 ps after excitation in the visible and NIR region. Fourier transform of the kinetic data reveal ∼0.18 and 0.40 THz low-frequency vibrations in aqueous AuNC solutions, with the latter attributed to coherent vibrations following hot electronic relaxation. A biphasic decay of the AuNC excited state on the microsecond timescales confirm their exceptionally long-lived lifetimes and that the photophysics is largely unaffected by the functional end group on the ligand. Finally, ultrafast studies of AuNCs coupled to the 625 QD donors reveal excited-state quenching and wavelength shifts of the QD’s ground-state bleach and the appearance of the excited state of the AuNC resulting from energy transfer occurring on the ∼200 ps timescale.

Inverse heavy-atom effect in near infrared photoluminescent gold nanoclusters.

Fluorophores functionalized with heavy elements show enhanced intersystem crossing due to increased spin-orbit coupling, which in turn shortens the fluorescence decay lifetime (τPL). This phenomenon is known as the heavy-atom effect (HAE). Here, we report the observation of increased τPL upon functionalisation of near-infrared photoluminescent gold nanoclusters with iodine. The heavy atom-mediated increase in τPL is in striking contrast with the HAE and referred to as inverse HAE. Femtosecond and nanosecond transient absorption spectroscopy revealed overcompensation of a slight decrease in lifetime of the transition associated with the Au core (ps) by a large increase in the long-lived triplet state lifetime associated with the Au shell, which contributed to the observed inverse HAE. This unique observation of inverse HAE in gold nanoclusters provides the means to enhance the triplet excited state lifetime.

Folic acid functionalized gold nanoclusters for enabling targeted fluorescence imaging of human ovarian cancer cells

Photoluminescent gold nanoclusters have attracted an extensive research interest in bioimaging and therapeutics due to several distinctive advantages such as high fluorescent photostability, good dispersibility, low toxicity and large Stokes shift. However, a better understanding of the correlation between optical properties in various environments and their uptake by specific cancer cells is still needed. Herein, we developed bovine serum albumin stabilized gold nanoclusters (BSA-AuNCs) with an intrinsic tunable photoluminescence emission in the first biological window. The as-synthetized BSA-AuNCs agents consists in protein polymerized-chains dopped with AuNCs with an average size of 2–3 nm and were found to exhibit relevant properties as high photostability, temperature-dependent and excitation induced tunable red photoluminescence. The photostable BSA-AuNCs were functionalized with folic acid (FA-BSA-AuNCs) in order to achieve for the first time an active targeting of NIH:OVCAR-3 human ovarian adenocarcinoma cells, via AuNCs, towards bioimaging applications. After confirming their biocompatibility up to a concentration of 40 mg/ml, the improved cellular uptake and staining ability of FA-BSA-AuNCs compared to the BSA-AuNCs was validated by conventional wide-field epi-fluorescence microscopy, while the intracellular localization was monitored by confocal fluorescence lifetime imaging microscopy (FLIM). Considering their valuable intrinsic photoluminescent properties, the synthesized FA-BSA-AuNCs hold great promise for direct application in cellular imaging as efficient contrast agents towards early cancer diagnosis and image-guided therapy of cancer.

Augmented interaction of multivalent arginine coated gold nanoclusters with lipid membranes and cells.

A library of ultra-small red photoluminescent gold nanoclusters (Au NCs) were synthesized with an increasing amount of positive charges provided by the addition of mono-, di- or trivalent-glutathione modified arginine peptides. We then studied how the arginine content impacted on the interaction of Au NCs with negatively charged artificial lipid bilayers and cell membranes. Results indicated that increasing the arginine content enhanced Au NCs' adsorption on lipid bilayers and on cell membranes followed by an increased cellular uptake in melanoma cells (COLO 829). Surprisingly, the presence of up to 40% serum for highly positively charged Au NCs did not hinder their interaction with lipid bilayers that contain glycolipids, suggesting a reduced opsonization of these Au NCs. In addition, these Au NCs are usually not toxic, except those with the highest arginine contents. Thus, controlled grafting of arginine peptides onto Au NCs is an elegant strategy to improve their binding and internalization by tumor cells while still keeping their anti-fouling properties.

Influence of the Spatial Conformation of Charged Ligands on the Optical Properties of Gold Nanoclusters

Photoluminescent gold nanoclusters (Au NCs) were synthesized in one step in aqueous conditions using a mixture of glutathione and (mono or multivalent) glutathione-modified arginine peptides. By controlling the ratio of coligands, we investigated how the multivalency and the amount of arginines influenced the growth of Au NCs, their surface chemistry, their colloidal stability, and their optical properties. We demonstrated using two-dimensional nuclear magnetic resonance spectroscopy that the organization of the ligand on the Au surface was composed by an inner rigid layer and an outer flexible part via inter- and/or intraligand spatial proximity. This directly impacted the structure of the Au NCs, as confirmed by gel electrophoresis, high-resolution transmission electron microscopy, diffusion-ordered spectroscopy, and mass spectrometry. Increasing arginine content also induced an increase of positive surface charge and an enhancement of the near infrared emission intensity at ∼670 nm with quantum yield u...

Surface Dynamics and Ligand-Core Interactions of Quantum Sized Photoluminescent Gold Nanoclusters.

Quantum-sized metallic clusters protected by biological ligands represent a new class of luminescent materials; yet the understanding of structural information and photoluminescence origin of these ultrasmall clusters remains a challenge. Herein we systematically study the surface ligand dynamics and ligand-metal core interactions of peptide-protected gold nanoclusters (AuNCs) with combined experimental characterizations and theoretical molecular simulations. We show that the peptide sequence plays an important role in determining the surface peptide structuring, interfacial water dynamics and ligand-Au core interaction, which can be tailored by controlling peptide acetylation, constituent amino acid electron donating/withdrawing capacity, aromaticity/hydrophobicity and by adjusting environmental pH. Specifically, emission enhancement is achieved through increasing the electron density of surface ligands in proximity to the Au core, discouraging photoinduced quenching, and by reducing the amount of surface-bound water molecules. These findings provide key design principles for understanding the surface dynamics of peptide-protected nanoparticles and maximizing the photoluminescence of metallic clusters through the exploitation of biologically relevant ligand properties.

Self-Assembled Chiral Gold Supramolecules with Efficient Laser Absorption for Enantiospecific Recognition of Carnitine.

Stereospecific recognition of chiral molecules is ubiquitous in chemical and biological systems, thus leading to strong demand for the development of enantiomeric drugs, enantioselective sensors, and asymmetric catalysts. In this study, we demonstrate the ratio of d-Cys and l-Cys playing an important role in determining the optical properties and the structures of self-assembled Cys-Au(I) supramolecules prepared through a simple reaction of tetrachloroaurate(III) with chiral cysteine (Cys). The irregularly shaped -[d-Cys-Au(I)] n- or - [l-Cys-Au(I)] n- supramolecules with a size larger than 500 nm possessing strong absorption in the near-UV region and chiroptical characteristics were only obtained from the reaction of Au(III) with d-Cys or l-Cys. On the other hand, spindle-shaped -[d/l-Cys-Au(I)] n- supramolecules were formed when using Au(III) with mixtures of d/l-Cys. Our results have suggested that Au(I)···Au(I) aurophilic interactions, and stacked hydrogen bonding and zwitterionic interactions between d/l-Cys ligands are important in determining their structures. The NaBH4-mediated reduction induces the formation of photoluminescent gold nanoclusters (Au NCs) embedded in the chiral -[d-Cys-Au(I)] n- or -[l-Cys-Au(I)] n- supramolecules with a quantum yield of ca. 10%. The as-formed Au NCs/-[d-Cys-Au(I)] n- and Au NCs/-[l-Cys-Au(I)] n- are an enantiospecific substrate that can trap l-carnitine and d-carnitine, respectively, and function as a nanomatrix for surface-assisted laser desorption/ionization mass spectrometry (LDI-MS). The high absorption efficiency of laser energy, analyte-binding capacity, and homogeneity of the Au NCs/-[Cys-Au(I)] n- allow for quantitation of enantiomeric carnitine down to the micromolar regime with high reproducibility. The superior efficiency of the Au NCs/-[d-Cys-Au(I)] n- substrate has been further validated by quantification of l-carnitine in dietary supplements with accuracy and precision. Our study has opened a new avenue for chiral quantitation of various analytes through LDI-MS using metal nanocomposites consisting of NCs and metal-ligand complexes.

Gold nanoclusters with bright near-infrared photoluminescence.

The increase in nonradiative pathways with decreasing emission energy reduces the luminescence quantum yield (QY) of near-infrared photoluminescent (NIR PL) metal nanoclusters. Efficient surface ligand chemistry can significantly improve the luminescence QY of NIR PL metal nanoclusters. In contrast to the widely reported but modestly effective thiolate ligand-to-metal core charge transfer, we show that metal-to-ligand charge transfer (MLCT) can be used to greatly enhance the luminescence QY of NIR PL gold nanoclusters (AuNCs). We synthesized water-soluble and colloidally stable NIR PL AuNCs with unprecedentedly high QY (∼25%) upon introduction of triphenylphosphonium moieties into the surface capping layer. By using a combination of spectroscopic and theoretical methods, we provide evidence for gold core-to-ligand charge transfer occurring in AuNCs. We envision that this work can stimulate the development of these unusually bright AuNCs for promising optoelectronic, bioimaging, and other applications.

Photocatalytic synthesis of intensely photoluminescent gold nanoclusters and application in cell imaging

In this article, a facile and rapid method was developed to synthesize intensely photoluminescent gold nanoclusters (AuNCs) based on photocatalytic reduction. Using (5-mercapto-1,3,4-thiadiazol-2-ylthio)acetic acid (TMT) that is a photosensitive material as the ligands, AuNC@TMT, with high photoluminescence quantum yield (19.7%), were prepared. The average diameter of gold core is 1.69 ± 0.22 nm. The maximum excitation and emission wavelengths of AuNC@TMT are at 422 and 516 nm, respectively. The mechanism of photocatalytic reduction is preliminarily understood. Under UV lamp with 365 nm irradiation, Au(Ι)-TMT complex occurred with electron transfer from TMT to Au(Ι), which was reduced to Au(0) as the gold core of AuNC. Thus, it indicates that the photosensitive and electron transport materials with a thiol group will be superior ligands for synthesis of intensely photoluminescent AuNCs.

Photoluminescent Gold Nanoclusters in Cancer Cells: Cellular Uptake, Toxicity, and Generation of Reactive Oxygen Species.

In recent years, photoluminescent gold nanoclusters have attracted considerable interest in both fundamental biomedical research and practical applications. Due to their ultrasmall size, unique molecule-like optical properties, and facile synthesis gold nanoclusters have been considered very promising photoluminescent agents for biosensing, bioimaging, and targeted therapy. Yet, interaction of such ultra-small nanoclusters with cells and other biological objects remains poorly understood. Therefore, the assessment of the biocompatibility and potential toxicity of gold nanoclusters is of major importance before their clinical application. In this study, the cellular uptake, cytotoxicity, and intracellular generation of reactive oxygen species (ROS) of bovine serum albumin-encapsulated (BSA-Au NCs) and 2-(N-morpholino) ethanesulfonic acid (MES)-capped photoluminescent gold nanoclusters (Au-MES NCs) were investigated. The results showed that BSA-Au NCs accumulate in cells in a similar manner as BSA alone, indicating an endocytotic uptake mechanism while ultrasmall Au-MES NCs were distributed homogeneously throughout the whole cell volume including cell nucleus. The cytotoxicity of BSA-Au NCs was negligible, demonstrating good biocompatibility of such BSA-protected Au NCs. In contrast, possibly due to ultrasmall size and thin coating layer, Au-MES NCs exhibited exposure time-dependent high cytotoxicity and higher reactivity which led to highly increased generation of reactive oxygen species. The results demonstrate the importance of the coating layer to biocompatibility and toxicity of ultrasmall photoluminescent gold nanoclusters.

Highly selective and sensitive nanoprobes for Hg(II) ions based on photoluminescent gold nanoclusters

We report a facile strategy to synthesize a novel fluorescent gold nanoclusters (NAC-AuNCs) in one step by using only the reactants of HAuCl4 and N-acetyl-l-cysteine. The as-prepared AuNCs exhibited a fluorescence emission at 590nm and a quantum yield of 13.6%. On the basis of metallophilic Hg2+–Au+ interaction-induced fluorescence quenching mechanism, the fluorescent NAC-AuNCs offer highly sensitivity with a limit of detection of 0.2nM for determination of Hg2+ ions, which is 50 times lower than the limit value (10nM) defined by the U.S. Environmental Protection Agency in drinkable water. The proposed fluorescent probe has a linear response range of 2.0–3200nM Hg2+ ions and good repeatable response to 20nM Hg2+ with a relative standard deviation of 3.2% (n=6). Also, the luminescence response of the NAC-AuNCs probe in the presence of EDTA is especially selective to Hg2+. The proposed method has been successfully applied for determination of Hg2+ in various water samples, and the results agreed well with those obtained by the ICP-AES method.

Photoinduced spectral changes of photoluminescent gold nanoclusters.

Ultrasmall photoluminescent gold nanoclusters (Au NCs), composed of several atoms with sizes up to a few nanometers, have recently stimulated extensive interest. Unique molecule-like behaviors, low toxicity, and facile synthesis make photoluminescent Au NCs a very promising alternative to organic fluorophores and semiconductor quantum dots (QDs) in broad ranges of biomedical applications. However, using gold nanoparticles (Au NPs) for bioimaging might cause their degradation under continuous excitation with UV light, which might result in toxicity. We report spectral changes of photoluminescent 2-(N-morpholino) ethanesulfonic acid (MES)-coated (Au-MES) NCs under irradiation with UV/blue light. Photoluminescent water soluble Au- MES NCs with a photoluminescence (PL) band maximum at 476 nm (λex = 420 nm) were synthesized. Under irradiation with 402 nm wavelength light the size of photoluminescent Au-MES NCs decreased (λem = 430 nm). Irradiating the sample solution with 330 nm wavelength light, nonluminescent Au NPs were disrupted, and photoluminescent Au NCs (λem = 476 nm) were formed. Irradiation with 330 nm wavelength light did not directly affect photoluminescent Au-MES NCs, however, increase in PL intensity indicated the formation of photoluminescent Au NCs from the disrupted nonluminescent Au NPs. This study gives a good insight into the photostability of MES-coated Au NPs under continuous excitation with UV/blue light.

Dextran-encapsulated photoluminescent gold nanoclusters: synthesis and application

Dextrans are widely used as additives in food, pharmaceutical, and cosmetics because of their hydrophilicity, biocompatibility, and low toxicity. These features allow the use of dextrans to modify the surface of nanoparticles to improve cell compatibility for biomedical applications. Additionally, dextran molecules covalently bound with fluorescent dyes are frequently used as tracers in animal studies. These facts show that dextrans are useful compounds for biomedicine-related applications and research. Our aim was to explore a facile way to generate dextran-derived nanoparticles with photoluminescent property for the use in fluorescence imaging of bacteria and cancer cells. Dextran-encapsulated gold nanoclusters (AuNCs@dextran) were generated through a one-pot reaction by stirring dextrans and aqueous tetrachloroauric acid overnight. The generated AuNCs exhibit bright and green photoluminescence under the illumination of an ultraviolet lamp (λ max = 365 nm), and high cell biocompatibility was found as well. Therefore, the generated AuNCs can be used as fluorescence tracers and nanoprobes. We explored the suitability of AuNCs@dextran as labeling agents for bacteria, such as Staphylococcus aureus and Escherichia coli. After the bacteria were labeled by AuNCs@dextran, they became quite visible under a fluorescence microscope. Additionally, we demonstrated that nanocomposites composed of AuNCs@dextran and silica beads can be readily internalized by cancer cells. The nanocomposites can be readily detected in the cells through their photoluminescence, suggesting possible applications in drug delivery and fluorescence imaging.

Photoluminescent Gold Nanoclusters as Sensing Probes for Uropathogenic Escherichia coli

Glycan-bound nanoprobes have been demonstrated as suitable sensing probes for bacteria containing glycan binding sites. In this study, we demonstrated a facile approach for generating glycan-bound gold nanoclusters (AuNCs). The generated AuNCs were used as sensing probes for corresponding target bacteria. Mannose-capped AuNCs (AuNCs@Mann) were generated and used as the model sensors for target bacteria. A one-step synthesis approach was employed to generate AuNCs@Mann. In this approach, an aqueous solution of tetrachloroauric acid and mannoside that functionized with a thiol group (Mann-SH) was stirred at room temperature for 48 h. The mannoside functions as reducing and capping agent. The size of the generated AuNCs@Mann is 1.95±0.27 nm, whereas the AuNCs with red photoluminescence have a maximum emission wavelength of ∼630 nm (λexcitation = 375 nm). The synthesis of the AuNCs@Mann was accelerated by microwave heating, which enabled the synthesis of the AuNCs@Mann to complete within 1 h. The generated AuNCs@Mann are capable of selectively binding to the urinary tract infection isolate Escherichia coli J96 containing the mannose binding protein FimH expressed on the type 1 pili. On the basis of the naked eye observation, the limit of detection of the sensing approach is as low as ∼2×106 cells/mL.