Smartphone-based low-cost and rapid quantitative detection of urinary creatinine with the Tyndall effect.

This research aims to develop a robust and quantitative method for measuring creatinine levels by harnessing the enhanced Tyndall effect (TE) phenomenon. The envisioned sensing assay is designed for practical deployment in resource-limited settings or homes, where access to advanced laboratory facilities is limited. Its primary objective is to enable regular and convenient monitoring of renal healthcare, particularly in cases involving elevated creatinine levels. The creatinine sensing strategy is achieved based on the aggregation of gold nanoparticles (AuNPs) triggered via the direct crosslinking reaction between creatinine and AuNPs, where an inexpensive laser pointer was used as a handheld light source and a smartphone as a portable device to record the TE phenomenon enhanced by the creatinine-induced aggregation of AuNPs. After evaluation and optimization of parameters such as AuNP concentrations and TE measurement time, the subsequent proof-of-concept experiments demonstrated that the average gray value change of TE images was linearly related to the logarithm of creatinine concentrations in the range of 1-50 µM, with a limit of detection of 0.084 µM. Meanwhile, our proposed creatinine sensing platform exhibited highly selective detection in complex matrix environments. Our approach offers a straightforward, cost-effective, and portable means of creatinine detection, presenting an encouraging signal readout mechanism suitable for point-of-care (POC) applications. The utilization of this assay as a POC solution exhibits potential for expediting timely interventions and enhancing healthcare outcomes among individuals with renal health issues.

Nanoscale engineering of gold particles in 18th century Böttger lusters and glazes.

SignificanceThe exploration of gold-based colorants in glass and glazes led Nobel Laureate Richard Zsigmondy to the study of colloids, and to the development, with Henry Siedentopf, of the earliest microscopes capable of resolving such small length scales. Zsigmondy's studies were preceded by alchemical investigations starting in the 17th century that yielded the gold-based Purple of Cassius, and experiments in the early 18th century resulting in an unusual purple iridescent porcelain overglaze, called Böttger luster, at the Meissen Manufactory. We discuss the first nano-scale characterization of Böttger luster, its successful replication, and propose an explanation for its optical properties based on the physics of scattering and interference of nanoparticle arrays.

Far-Field Petahertz Sampling of Plasmonic Fields.

The response of metal nanostructures to optical excitation leads to localized surface plasmon (LSP) generation with nanoscale field confinement driving applications in, for example, quantum optics and nanophotonics. Field sampling in the terahertz domain has had a tremendous impact on the ability to trace such collective excitations. Here, we extend such capabilities and introduce direct sampling of LSPs in a more relevant petahertz domain. The method allows to measure the LSP field in arbitrary nanostructures with subcycle precision. We demonstrate the technique for colloidal nanoparticles and compare the results to finite-difference time-domain calculations, which show that the build-up and dephasing of the plasmonic excitation can be resolved. Furthermore, we observe a reshaping of the spectral phase of the few-cycle pulse, and we demonstrate ad-hoc pulse shaping by tailoring the plasmonic sample. The methodology can be extended to single nanosystems and applied in exploring subcycle, attosecond phenomena.

Customized Self-Assembled Gold Nanoparticle-DNA Origami Composite Templates for Shape-Directed Growth of Plasmonic Structures.

The metal plasmonic nanostructure has the optical property of plasmon resonance, which holds great potential for development in nanophotonics, bioelectronics, and molecular detection. However, developing a general and straightforward method to prepare metal plasmonic nanostructures with a controllable size and morphology still poses a challenge. Herein, we proposed a synthesis strategy that utilized a customizable self-assembly template for shape-directed growth of metal structures. We employed gold nanoparticles (AuNPs) as connectors and DNA nanotubes as branches, customizing gold nanoparticle-DNA origami composite nanostructures with different branches by adjusting the assembly ratio between the connectors and branches. Subsequently, various morphologies of plasmonic metal nanostructures were created using this template shape guided strategy, which exhibited enhancement of surface-enhanced Raman scattering (SERS) signals. This strategy provides a new approach for synthesizing metallic nanostructures with multiple morphologies and opens up another possibility for the development of customizable metallic plasmonic structures with broader applications.

Coupling Gold Nanospheres into Nanochain Constructs for High-Contrast, Longitudinal Photoacoustic Imaging.

Structural parameters play a crucial role in determining the electromagnetic and thermal responses of gold nanoconstructs (GNCs) at near-infrared (NIR) wavelengths. Therefore, developing GNCs for reliable, high-contrast photoacoustic imaging has been focused on adjusting structural parameters to achieve robust NIR light absorption with photostability. In this study, we introduce an efficient photoacoustic imaging contrast agent: gold sphere chains (GSCs) consisting of plasmonically coupled gold nanospheres. The chain geometry results in enhanced photoacoustic signal generation originating from outstanding photothermal characteristics compared to traditional gold contrast agents, such as gold nanorods. Furthermore, the GSCs produce consistent photoacoustic signals at laser fluences within the limits set by the American National Standards Institute. The exceptional photoacoustic response of GSCs allows for high-contrast photoacoustic imaging over multiple imaging sessions. Finally, we demonstrate the utility of our GSCs for molecular photoacoustic cancer imaging, both in vitro and in vivo, through the integration of a tumor-targeting moiety.

Direct Observation of the Reactivity of Electrons toward Gold Nanoparticles in Aqueous Solution.

The catalytic activity of gold nanoparticles (AuNPs) has been widely acknowledged; however, Au NPs are considered to be highly inert as radiosensitizers in biological systems. This apparent discrepancy across different fields complicates the understanding of their interfacial reactivity, particularly in terms of electron transfer reactions. Here, we employ pulse radiolysis to determine the rate constants for the reactions of electrons with AuNPs in aqueous solution. Our investigation of AuNPs with different sizes and surface modifications demonstrates the potential influence of the AuNPs design on electron transfer reactions. These findings address long-standing mechanistic contradictions and underscore the significance of interfacial electron dynamics on AuNPs in both catalytic and biological processes.

Rate-Engineered Plasmon-Enhanced Fluorescence for Real-Time Microsecond Dynamics of Single Biomolecules.

Single-molecule fluorescence has revealed a wealth of biochemical processes but does not give access to submillisecond dynamics involved in transient interactions and molecular dynamics. Here we overcome this bottleneck and demonstrate record-high photon count rates of >107 photons/s from single plasmon-enhanced fluorophores. This is achieved by combining two conceptual novelties: first, we balance the excitation and decay rate enhancements by the antenna's volume, resulting in maximum fluorescence intensity. Second, we enhance the triplet decay rate using a multicomponent surface chemistry that minimizes microsecond blinking. We demonstrate applications to two exemplary molecular processes: we first reveal transient encounters and hybridization of DNA with a 1 µs temporal resolution. Second, we exploit the field gradient around the nanoparticle as a molecular ruler to reveal microsecond intramolecular dynamics of multivalent complexes. Our results pave the way toward real-time microsecond studies of biochemical processes using an implementation compatible with existing single-molecule fluorescence methods.

Charged Gold Nanoparticles for Target Identification-Alignment and Automatic Segmentation of CT Image-Guided Adaptive Radiotherapy in Small Hepatocellular Carcinoma.

Because of the challenges posed by anatomical uncertainties and the low resolution of plain computed tomography (CT) scans, implementing adaptive radiotherapy (ART) for small hepatocellular carcinoma (sHCC) using artificial intelligence (AI) faces obstacles in tumor identification-alignment and automatic segmentation. The current study aims to improve sHCC imaging for ART using a gold nanoparticle (Au NP)-based CT contrast agent to enhance AI-driven automated image processing. The synthesized charged Au NPs demonstrated notable in vitro aggregation, low cytotoxicity, and minimal organ toxicity. Over time, an in situ sHCC mouse model was established for in vivo CT imaging at multiple time points. The enhanced CT images processed using 3D U-Net and 3D Trans U-Net AI models demonstrated high geometric and dosimetric accuracy. Therefore, charged Au NPs enable accurate and automatic sHCC segmentation in CT images using classical AI models, potentially addressing the technical challenges related to tumor identification, alignment, and automatic segmentation in CT-guided online ART.

Nanomaterial-Enabled Photothermal Heating and Its Use for Cancer Therapy via Localized Hyperthermia.

Photothermal therapy (PTT), which employs nanoscale transducers delivered into a tumor to locally generate heat upon irradiation with near-infrared light, shows great potential in killing cancer cells through hyperthermia. The efficacy of such a treatment is determined by a number of factors, including the amount, distribution, and dissipation of the generated heat, as well as the type of cancer cell involved. The amount of heat generated is largely controlled by the number of transducers accumulated inside the tumor, the absorption coefficient and photothermal conversion efficiency of the transducer, and the irradiance of the light. The efficacy of treatment depends on the distribution of the transducers in the tumor and the penetration depth of the light. The vascularity and tissue thermal conduction both affect the dissipation of heat and thereby the distribution of temperature. The successful implementation of PTT in the clinic setting critically depends on techniques for real-time monitoring and management of temperature.

Gold Nanoparticles Capped with a Novel Titanium(IV)-Containing Polyoxomolybdate Cluster: Selective and Enhanced Bactericidal Effect Against Escherichia coli.

Bacterial infections are a public health threat of increasing concern in medical care systems; hence, the search for novel strategies to lower the use of antibiotics and their harmful effects becomes imperative. Herein, the antimicrobial performance of four polyoxometalate (POM)-stabilized gold nanoparticles (Au@POM) against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) as Gram-negative and Gram-positive bacteria models, respectively, is studied. The bactericidal studies performed, both in planktonic and sessile forms, evidence the antimicrobial potential of these hybrid nanostructures with selectivity toward Gram-negative species. In particular, the Au@GeMoTi composite with the novel [Ti2 (HGeMo7 O28 )2 ]10- POM capping ligand exhibits outstanding bactericidal efficiency with a minimum inhibitory concentration of just 3.12 µm for the E. coli strain, thus outperforming the other three Au@POM counterparts. GeMoTi represents the fourth example of a water-soluble TiIV -containing polyoxomolybdate, and among them, the first sandwich-type structure having heteroatoms in high-oxidation state. The evaluation of the bactericidal mechanisms of action points to the cell membrane hyperpolarization, disruption, and subsequent nucleotide leakage and the low cytotoxicity exerted on five different cell lines at antimicrobial doses demonstrates the antibiotic-like character. These studies highlight the successful design and development of a new POM-based nanomaterial able to eradicate Gram-negative bacteria without damaging mammalian cells.

Biomolecular Corona of Gold Nanoparticles: The Urgent Need for Strong Roots to Grow Strong Branches.

Gold nanoparticles (GNPs) are largely employed in diagnostics/biosensors and are among the most investigated nanomaterials in biology/medicine. However, few GNP-based nanoformulations have received FDA approval to date, and promising in vitro studies have failed to translate to in vivo efficacy. One key factor is that biological fluids contain high concentrations of proteins, lipids, sugars, and metabolites, which can adsorb/interact with the GNP's surface, forming a layer called biomolecular corona (BMC). The BMC can mask prepared functionalities and target moieties, creating new surface chemistry and determining GNPs' biological fate. Here, the current knowledge is summarized on GNP-BMCs, analyzing the factors driving these interactions and the biological consequences. A partial fingerprint of GNP-BMC analyzing common patterns of composition in the literature is extrapolated. However, a red flag is also risen concerning the current lack of data availability and regulated form of knowledge on BMC. Nanomedicine is still in its infancy, and relying on recently developed analytical and informatic tools offers an unprecedented opportunity to make a leap forward. However, a restart through robust shared protocols and data sharing is necessary to obtain "stronger roots". This will create a path to exploiting BMC for human benefit, promoting the clinical translation of biomedical nanotools.

Multifunctional Gold Nanozyme-Engineered Amphotericin B for Enhanced Antifungal Infection Therapy.

Chronic wounds of significant severity and acute injuries are highly vulnerable to fungal infections, drastically impeding the expected wound healing trajectory. The clinical use of antifungal therapeutic drug is hampered by poor solubility, high toxicity and adverse reactions, thereby necessitating the urgent development of novel antifungal therapy strategy. Herein, this study proposes a new strategy to enhance the bioactivity of small-molecule antifungal drugs based on multifunctional metal nanozyme engineering, using amphotericin B (AmB) as an example. AmB-decorated gold nanoparticles (AmB@AuNPs) are synthesized by a facile one-pot reaction strategy, and the AmB@AuNPs exhibit superior peroxidase (POD)-like enzyme activity, with maximal reaction rates (Vmax) 3.4 times higher than that of AuNPs for the catalytic reaction of H2O2. Importantly, the enzyme-like activity of AuNPs significantly enhanced the antifungal properties of AmB, and the minimum inhibitory concentrations of AmB@AuNPs against Candida albicans (C. albicans) and Saccharomyces cerevisiae (S. cerevisiae) W303 are reduced by 1.6-fold and 50-fold, respectively, as compared with AmB alone. Concurrent in vivo studies conducted on fungal-infected wounds in mice underscored the fundamentally superior antifungal ability and biosafety of AmB@AuNPs. The proposed strategy of engineering antifungal drugs with nanozymes has great potential for enhanced therapy of fungal infections and related diseases.

Hybrid Nanogel-Wrapped Anisotropic Gold Nanoparticles Feature Enhanced Photothermal Stability.

Anisotropic gold nanoparticles (AuNPs) are renowned for their unique properties - including localized surface plasmon resonance (LSPR) and adjustable optical responses to light exposure - that enable the conversion of light into heat and make them a promising tool in cancer therapy. Nonetheless, their tendency to aggregate and consequently lose their photothermal conversion capacity during prolonged irradiation periods represents a central challenge in developing anisotropic AuNPs for clinical use. To overcome this issue, an innovative approach that facilitates the encapsulation of individual anisotropic AuNPs within thin nanogels, forming hybrid nanomaterials that mirror the inorganic core's morphology while introducing a negligible (2-8 nm) increase in overall diameter is proposed. The encapsulation of rod- and star-shaped anisotropic AuNPs within poly-acrylamide (pAA) or poly-(N-isopropylacrylamide) (pNIPAM) nanogels is successfully demonstrated. The ultrathin polymeric layers display remarkable durability, significantly enhancing the photothermal stability of anisotropic AuNPs during their interaction with near-infrared light and effectively boosting their photothermal capacities for extended irradiation periods. The outcomes of the research thus support the development of more stable and reliable AuNPs as hybrid nanomaterials, positioning them as promising nanomedicinal platforms.

Nanostructure Tuning of Gold Nanoparticles Films via Click Sintering.

Colloidal metal nanoparticles dispersions are commonly used to create functional printed electronic devices and they typically require time-, energy- and equipment-consuming post-treatments to improve their electrical and mechanical properties. Traditional methods, e.g. thermal, UV/IR, and microwave treatments, limit the substrate options and may require expensive equipment, not available in all the laboratories. Moreover, these processes also cause the collapse of the film (nano)pores and interstices, limiting or impeding its nanostructuration. Finding a simple approach to obtain complex nanostructured materials with minimal post-treatments remains a challenge. In this study, a new sintering method for gold nanoparticle inks that called as "click sintering" has been reported. The method uses a catalytic reaction to enhance and tune the nanostructuration of the film while sintering the metallic nanoparticles, without requiring any cumbersome post-treatment. This results in a conductive and electroactive nanoporous thin film, whose properties can be tuned by the conditions of the reaction, i.e., concentration of the reagent and time. Therefore, this study presents a novel and innovative one-step approach to simultaneously sinter gold nanoparticles films and create functional nanostructures, directly and easily, introducing a new concept of real-time treatment with possible applications in the fields of flexible electronics, biosensing, energy, and catalysis.

Fluorescent Noncovalent Organic Framework for Supporting Gold Nanoparticles as Heterogeneous Catalyst with Merits of Easy Detection and Recycle.

A porous noncovalent organic framework with AIE effect is designed and synthesized as the support for gold nanoparticles (AuNPs). The framework is fabricated through the electrostatic complexation between carboxymethyl cellulose and tetraphenylethene-containing ammonium surfactant, which can complex AuNPs via the noncovalent interactions to offer a heterogeneous catalyst. Compared to the covalent modification on cellulose, this noncovalent framework gains superiorities in the catalyst synthesis and the size control of AuNPs. The AIE property and water-insolubility allow such heterogeneous catalysts to be easily detected, separated, and recycled, opening a new pathway for the reduction of nitrobenzene compounds and some dye compounds in aqueous conditions, which present the features of green chemistry. The use of cellulose for developing new heterogeneous metal catalysts, especially in a noncovalent way, would promote the value-added utilization of cellulose. This work provides a design strategy for gaining heterogeneous metal catalysts by taking advantage of natural bioresources.

Size-Dependent Penetration of Nanoparticles in Tumor Spheroids: A Multidimensional and Quantitative Study of Transcellular and Paracellular Pathways.

Tumor penetration of nanoparticles is crucial in nanomedicine, but the mechanisms of tumor penetration are poorly understood. This work presents a multidimensional, quantitative approach to investigate the tissue penetration behavior of nanoparticles, with focuses on the particle size effect on penetration pathways, in an MDA-MB-231 tumor spheroid model using a combination of spectrometry, microscopy, and synchrotron beamline techniques. Quasi-spherical gold nanoparticles of different sizes are synthesized and incubated with 2D and 3D MDA-MB-231 cells and spheroids with or without an energy-dependent cell uptake inhibitor. The distribution and penetration pathways of nanoparticles in spheroids are visualized and quantified by inductively coupled plasma mass spectrometry, two-photon microscopy, and synchrotron X-ray fluorescence microscopy. The results reveal that 15 nm nanoparticles penetrate spheroids mainly through an energy-independent transcellular pathway, while 60 nm nanoparticles penetrate primarily through an energy-dependent transcellular pathway. Meanwhile, 22 nm nanoparticles penetrate through both transcellular and paracellular pathways and they demonstrate the greatest penetration ability in comparison to other two sizes. The multidimensional analytical methodology developed through this work offers a generalizable approach to quantitatively study the tissue penetration of nanoparticles, and the results provide important insights into the designs of nanoparticles with high accumulation at a target site.

Ligand Mediation for Tunable and Oxide Suppressed Surface Gold-Decorated Liquid Metal Nanoparticles.

Gallium-based liquid metal systems hold vast potential in materials science. However, maximizing their possibilities is hindered by gallium's native oxide and interfacial functionalization. In this study, small-molecule ligands are adopted as surfactants to modify the surface of eutectic gallium indium (EGaIn) nanoparticles and suppress oxidation. Different p-aniline derivatives are explored. Next, the reduction of chloroanric acid (HAuCl4 ) onto these p-aniline ligand modified EGaIn nanoparticles is investigated to produce gold-decorated EGaIn nanosystems. It is found that by altering the concentrations of HAuCl4 or the p-aniline ligand, the formation of gold nanoparticles (AuNPs) on EGaIn can be manipulated. The reduction of interfacial oxidation and presence of AuNPs enhances electrical conductivity, plasmonic performance, wettability, stability, and photothermal performance of all the p-aniline derivative modified EGaIn. Of these, EGaIn nanoparticles covered with the ligand of p-aminobenzoic acid offer the most evenly distributed AuNPs decoration and perfect elimination of gallium oxides, resulting in the augmented electrical conductivity, and highest wettability suitable for patterning, enhanced aqueous stability, and favorable photothermal properties. The proof-of-concept application in photothermal therapy of cancer cells demonstrates significantly enhanced photothermal conversion performance along with good biocompatibility. Due to such unique characteristics, the developed gold-decorated EGaIn nanodroplets are expected to offer significant potential in precise medicine.

Efficient Photothermal Sensor Based on Coral-Like Hollow Gold Nanospheres for the Sensitive Detection of Sulfonamides.

Gold nanoparticles (AuNPs), universally regarded as colorimetric signal reporters, are widely employed in lateral flow immunoassays (LFIAs). However, it is difficult for AuNPs-LFIA to achieve a wide range and sensitive detection. Herein, novel coral-like hollow gold nanospheres (CHGNPs) are synthesized. The growth of gold nanospheres can be regulated to obtain a multibranched and hollow construction. The obtained CHGNPs possess intense broadband absorption across the visible to near-infrared region, exhibiting a high molar extinction coefficient of 14.65 × 1011 M-1 cm-1 and a photothermal conversion efficiency of 79.75%. Thus, the photothermal/colorimetric dual-readout LFIA is developed based on CHGNPs (CHGNPs-PT-LFIA and CHGNPs-CM-LFIA) to effectively improve the detection sensitivity and broaden the detection range in regard to sulfonamides (SAs). The limits of detection of the CHGNPs-PT-LFIA and CHGNPs-CM-LFIA reached 1.9 and 2.8 pg mL-1 for the quantitative detection of sulfaquinoxaline, respectively, which are 6.3-fold and 4.3-fold lower than that of the AuNPs-LFIA. Meanwhile, the CHGNPs-PT-LFIA broadened the detection range to three orders of magnitude, which ranged from 2.5 to 5000 pg mL-1. The synthesized photothermal CHGNPs have been proven effective in improving the performance of the LFIA and provide a potential option for the construction of sensing platforms.

Diffusion Coefficients of Coated Plasmonic Nanoparticles in Viscous Environment.

The Stokes-Einstein relationship (SER) is not valid anymore in polymeric solutions for nanoparticles. It is thus important to characterize their diffusion properties to get a finer understanding of their behavior and to better tune their attributes for biomedical applications. The diffusion of gold and silver nanoparticles with citrate, hyaluronic acid, methyl-polyethylene glycol, and antibody-polyethylene glycol coatings is studied in hyaluronic-based viscous solutions. The diffusion coefficient D is estimated from the Brownian motion thanks to a cost-effective side-illumination device. It is determined that the nanoparticles (hydrodynamic radius rh: 30-135 nm) diffuse up to 4-5 times faster than expected using the SER with a macroscopic viscosity from 1 to 30 mPa·s. It is shown that the adapted Huggins equation is a good model to describe the diffusion behavior of nanoparticles using an effective viscosity ηeff given by l n ( η e f f η s ) = k ( R e f f E ) a $ln\ ( {\frac{{{{\eta }_{eff}}}}{{{{\eta }_s}}}} ) = \ k{{( {\ \frac{{{{R}_{eff}}}}{E}} )}^a}$ where R e f f - 2 = r h - 2 + R h - 2 $R_{eff}^{ - 2} = r_h^{ - 2}\ + R_h^{ - 2}$ where E is the polymer correlation length, Rh the polymer hydrodynamic radius and ηs the solvent viscosity. The values of k and a are given and allow to obtain D with an error of 10-20%. The impact of chemical interactions on the model parameter values are also highlighted, especially due to electrostatic interactions between the polymer and the nanoparticles.

Nanoporous Submicron Gold Particles Enable Nanoparticle-Based Localization Optoacoustic Tomography (nanoLOT).

Localization optoacoustic tomography (LOT) has recently emerged as a transformative super-resolution technique breaking through the acoustic diffraction limit in deep-tissue optoacoustic (OA) imaging via individual localization and tracking of particles in the bloodstream. However, strong light absorption in red blood cells has previously restricted per-particle OA detection to relatively large microparticles, ≈5 µm in diameter. Herein, it is demonstrated that submicron-sized porous gold nanoparticles, ≈600 nm in diameter, can be individually detected for noninvasive super-resolution imaging with LOT. Ultra-high-speed bright-field microscopy revealed that these nanoparticles generate microscopic plasmonic vapor bubbles, significantly enhancing opto-acoustic energy conversion through a nano-to-micro size transformation. Comprehensive in vitro and in vivo tests further demonstrated the biocompatibility and biosafety of the particles. By reducing the detectable particle size by an order of magnitude, nanoLOT enables microangiographic imaging with a significantly reduced risk of embolisms from particle aggregation and opens new avenues to visualize how nanoparticles reach vascular and potentially extravascular targets. The performance of nanoLOT for non-invasive imaging of microvascular networks in the murine brain anticipates new insights into neurovascular coupling mechanisms and longitudinal microcirculatory changes associated with neurodegenerative diseases.