Strategic framework for harnessing luminescent metal nanocluster assemblies in biosensing applications.

The distinctive physicochemical attributes of ultra-small metal nanoclusters (MNCs) resembling those of molecules make them versatile constituents for self-assembled frameworks. This critical review scrutinizes the influence of assembly on the photoluminescence (PL) properties of MNCs and investigates their utility in biosensing applications. The investigation is initiated with an assessment of the shift from individual MNCs to assemblies and its repercussions on PL efficacy. Subsequently, two distinct biosensing modalities are explored: assembly-driven detection mechanisms and detection predicated on structural modifications in assembled MNCs. Through meticulous examination, we underscore the potential of self-assembly methodologies in tailoring the PL behavior of MNCs for the detection of diverse biological analytes and diseases.

Biocompatible functionalisation of nanoclays for improved environmental remediation.

Among the wide range of materials used for remediating environmental contaminants, modified and functionalised nanoclays show particular promise as advanced sorbents, improved dispersants, or biodegradation enhancers. However, many chemically modified nanoclay materials are incompatible with living organisms when they are used in natural systems with detrimental implications for ecosystem recovery. Here we critically review the pros and cons of functionalised nanoclays and provide new perspectives on the synthesis of environmentally friendly varieties. Particular focus is given to finding alternatives to conventional surfactants used in modified nanoclay products, and to exploring strategies in synthesising nanoclay-supported metal and metal oxide nanoparticles. A large number of promising nanoclay-based sorbents are yet to satisfy environmental biocompatibility in situ but opportunities are there to tailor them to produce "biocompatible" or regenerative/reusable materials.

Probing the Microporous Structure of Silica Shell Via Aggregation-Induced Emission in Au(I)-Thiolate@SiO2 Nanoparticle.

An efficient method to investigate the window size of the silica shell generated via the classical Stöber method is reported by making use of the unique aggregation-induced emission property of Au(I)-thiolate complexes, which can precisely probe the porosity of the silica shell in Au(I)-thiolate@SiO2 nanoparticles.

Functionalization of metal nanoclusters for biomedical applications.

Metal nanoclusters (NCs) are emerging as a new class of functional nanomaterials in the area of biological sensing, labelling, imaging and therapy due to their unique physical and chemical properties, such as ultrasmall size, HOMO-LUMO transition, strong luminescence together with good photostability and biocompatibility. A recent surge of interest in this field is the surface functionalization of these metal NCs through which one can tailor their physicochemical properties, such as stability in solution, and strong luminescence, as well as their biodistribution and toxicity in biological systems, which in turn can empower these functionalized NCs with desirable targeting, imaging, and therapeutic ability for biomedical applications. In this review, we first introduce the functionalization strategies for the metal NCs developed in the past few years, followed by highlighting some biomedical applications of these functionalized metal NCs. We then discuss the difference of in vitro and in vivo fate as well as toxicity between various functionalized metal NCs. Finally, we present a short discussion on the current challenges and provide an outlook of the future developments of these functional metal NCs.

Molecular Packing-Driven Manipulation of Aggregation Induced Emission in Gold Nanoclusters.

A key limitation of supramolecular force-driven molecular assembly in aggregation-induced emission (AIE) materials is the need to precisely regulate molecular interactions within the assembly. Achieving such assemblies with in situ manipulable molecular arrangements could provide valuable insights into the role of molecular forces in AIE. Herein, by using glutathione-protected gold nanoclusters (AuNCs) as a model AIE material and a naturally occurring polyphenol, tannic acid (TA), as the assembling agent, we demonstrate that assemblies dominated by covalent bonds and hydrogen bonding show enhanced AIE, while those dominated by π-π stacking promote charge transfer, resulting in significant photoluminescence (PL) quenching. This phenomenon primarily stems from the oxidation of TA into smaller aromatic ring structures, leading to an increase in π-π interactions. The complete in situ oxidation of TA within the assembly induces a morphological transition from 3-D spherical to 2-D sheet-like structures due to the dominance of π-π interactions, consequently resulting in complete PL quenching of AuNCs. These findings highlight the critical role of molecular packing in modulating the AIE properties of AuNCs.

Unravelling structural insights into ligand-induced photoluminescence mechanisms of sulfur dots.

Sulfur dots (S-QDs) hold promise as a new category of metal-free, luminescent nanomaterials, yet their practical application faces challenges primarily due to a limited understanding of their structure and its impact on their optical properties. Herein, by employing a spectrum of aliphatic and aromatic ligands, we identify the surface structure and composition of S-QDs while delineating the pivotal role of ligands in inducing photoluminescence. Thiol-functionalized ligands, such as 4-mercapto benzoic acid and glutathione, notably promote the formation of both green and blue luminescent S-QDs, boosting a high quantum yield of up to 56%. Further investigation on the synthesis of S-QDs with 4-mercapto benzoic acid unveils the dual role of H2O2: etching sulfur powder and oxidizing the -SH group to -SO2H. These oxidized ligands passivate the S-QD surface through hydrogen bonding. Electrospray ionization mass spectrometry analysis unveils the presence of distinct sulfur species such as [S4(C6H5SO2H)4(H2O)2H]+ and [S6(C6H5SO2H)6(H2O)3H]+, while XPS analysis confirms the existence of zerovalent sulfur and oxidized sulfur species including SO32- and SO42-. Further detailed spectroscopic examination demonstrates that S-QDs predominantly exist as aggregated entities, with the emission wavelength correlating with the degree of aggregation. The absence of photoluminescence in aggregations devoid of ligands underscores the critical role of ligands in the photoluminescence genesis of S-QDs.

A potential carcinogenic pyrene derivative under Förster resonance energy transfer to various energy acceptors in nanoscopic environments.

Picosecond-resolved Förster resonance energy transfer (FRET) from various vibronic bands in benzo[a]pyrene (BP) shows a strong dependency on the spectral overlap of an energy acceptor in a confined environment. Our study on the dipolar interactions between BP and different acceptors, including ethidium (Et), acridine orange (AO), and crystal violet (CV), at the surface of a model anionic micelle revealed that the Förster distance (R0) and the rate of energy transfer is dependent on the individual spectral overlap of the vibronic bands of BP with the absorption spectra of the different energy acceptors. The differential behavior of the vibronic bands is compared with that of different dyes [quantum dots (QDs)] in a "dye-blend" (mixture) under FRET to an energy acceptor. Comparison of the FRET of the QDs with that of BP confirmed the independent nature of the dipolar interaction of the vibronic bands with other organic molecules, and the use of deconvolution techniques in the interpretation of the donor-acceptor (D-A) distance was also justified. We also showed that the consideration of differential FRET from the vibronic bands of BP and from the QDs in the dye-blend is equally acceptable in theoretical frameworks including the Infelta-Tachiya model and D-A distribution analysis in nanoenvironments.

MoS2 nanocrystals confined in a DNA matrix exhibiting energy transfer.

We report the wet chemical synthesis of MoS2 nanocrystals (NCs), a transition-metal dichalcogenide, using DNA as a host matrix. As evidenced from transmission electron microscopy (TEM), the NCs are highly crystalline, with an average diameter of ~5 nm. Ultraviolet-visible (UV-vis) absorption studies along with band gap calculations confirm that NCs are in quantum confinement. A prominent red shift of the optical absorption bands has been observed upon formation of the thin film using hexadecyltrimethylammonium chloride (CTAC), i.e., in the case of MoS2@DNA-CTAC. In the thin film, strong electron-phonon coupling arises because of the resonance effect, which is reflected from the emergence of intense first-, second-, and third-order Raman peaks, whenever excited with the 488 nm line. We have established that our as-synthesized MoS2 NCs quench the fluorescence of a well-known DNA minor groove binding probe, Hoechst 33258. Unprecedented fluorescence quenching (94%) of donor (Hoechst 33258) emission and efficient energy transfer (89%) between Hoechst 33258 and MoS2 NCs (acceptor) are obtained. The donor-acceptor distance of these conjugates has been described by a Förster resonance energy transfer (FRET)-based model. Furthermore, employing a statistical method, we have estimated the probability of the distance distribution between the donor and acceptor. We believe that the study described herein may enable substantial advances in fields of optoelectronics, photovoltaics, catalysis, and many others.

In Situ Depletion-Guided Engineering of Nanoshell-like Gold Nanocluster Assemblies with Enhanced Peroxidase-like Nanozyme Activity.

Functional superstructures constructed from metal nanoclusters (MNCs) hold great promise in providing highly tunable photoluminescence (PL), catalytic activity, photothermal stability, and biological functionality. However, their controlled synthesis with well-defined size, structure, and properties remains a significant challenge. Herein, we introduce a novel approach that combines depletion attraction and thermal activation to induce the in situ formation of spherical superclusters (AuSCs) from Au(I)-thiolate complexes within the assembly. Extensive characterization and electron tomographic reconstruction reveal that Au(I)-thiolate complexes can be sequentially transitioned into metallic Au0, resulting in hollow nanoshell-like structures with consistent size (∼110 nm) and diverse shell configurations. Our results demonstrate that AuSCs with thinner shells, containing a high concentration of Au(I)-thiolate complexes, exhibit the highest PL, while AuSCs with thicker shells, containing high concentrations of metallic gold atoms and low ligand density, show remarkable peroxidase-like nanozyme activity in the 3,3',5,5'-tetramethylbenzidine (TMB) oxidation reaction.

Protein-directed synthesis of NIR-emitting, tunable HgS quantum dots and their applications in metal-ion sensing.

The development of luminescent mercury sulfide quantum dots (HgS QDs) through the bio-mineralization process has remained unexplored. Herein, a simple, two-step route for the synthesis of HgS quantum dots in bovine serum albumin (BSA) is reported. The QDs are characterized by UV-vis spectroscopy, Fourier transform infrared (FT-IR) spectroscopy, luminescence, Raman spectroscopy, transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), circular dichroism (CD), energy dispersive X-ray analysis (EDX), and picosecond-resolved optical spectroscopy. Formation of various sizes of QDs is observed by modifying the conditions suitably. The QDs also show tunable luminescence over the 680-800 nm spectral regions, with a quantum yield of 4-5%. The as-prepared QDs can serve as selective sensor materials for Hg(II) and Cu(II), based on selective luminescence quenching. The quenching mechanism is found to be based on Dexter energy transfer and photoinduced electron transfer for Hg(II) and Cu(II), respectively. The simple synthesis route of protein-capped HgS QDs would provide additional impetus to explore applications for these materials.

Switchable catalysis and CO2 sensing by reduction resistant, luminescent copper-thiolate complexes.

Metal-thiolate complexes have been the focus of research for several years because of their unique photophysical properties and their use as a precursor for synthesizing various well-defined metal nanoclusters. A rational understanding of their structure-property relationship is necessary to realize their full potential in practical applications. Herein, we demonstrate the synthesis of a unique copper-thiolate complex with reversibly switchable catalytic and photoluminescence (PL) properties. The as-synthesized complex at basic pH (Complex B) showed cyan PL with a strong peak at ∼488 nm (cyan) and a small shoulder peak at ∼528 nm (green). When the pH of the complex was changed to acidic (Complex A), the PL was switched to light green. Such pH-responsive PL properties were demonstrated to be useful for pH and CO2 sensing. The switchable properties originate from their two distinct structural states at two different pHs. We found that Complex A was resistant to high concentrations of a strong reducing agent, and had an intermediate oxidation state of copper (Cu+) with good thermodynamic stability. Furthermore, the switchable catalytic property was investigated with a 4-nitrophenol reduction and 3,3',5,5'-tetramethylbenzidine (TMB) oxidation reaction. The reduction kinetics followed pseudo-first-order, where the catalytic activity was enhanced by more than 103 times when Complex B was switched to Complex A. A similar trend was also observed for TMB oxidation. Our design strategy demonstrates that redox switchable metal-thiolate complexes could be a powerful candidate for a plethora of applications.

Engineering Au Nanoclusters for Relay Luminescence Enhancement with Aggregation-Induced Emission.

The research of aggregation-induced emission (AIE) has been growing rapidly for the design of highly luminescent materials, as exemplified by the library of AIE-active materials (or AIEgens) fabricated and explored for diverse applications in different fields. Herein, we reported a relay luminescence enhancement of luminescent Au nanoclusters (Au NCs) through AIE. In addition, we demonstrated the emergence of reduced aggregation-caused luminescence by adjusting the temperature of the Au NC solution. The key to induce this effect is to attach a thermosensitive polymer poly(N-isopropylacrylamide) (PNIPAAm) on the surface of Au NCs, which will shrink at high temperature. More interestingly, the as-synthesized Au NCs-PNIPAAm can self-assemble into vesicles, resulting in an obvious decrease in the luminescence intensity in aqueous solution. The combination of relay luminescence enhancement (by AIE) and luminescence decrease (induced by thermosensitive polymers) will be beneficial to the understanding and manipulation of the optical properties of Au NCs, paving the way for their practical applications.

Depletion Driven Assembly of Ultrasmall Metal Nanoclusters: From Kinetically Arrested Assemblies to Thermodynamically Stable, Spherical Superclusters.

Nanoscale assembly of ultrasmall metal nanoclusters (MNCs) by means of molecular forces has proven to be a powerful strategy to engineer their molecule-like properties in multiscale dimensions. By leveraging depletion attraction as the guiding force, herein, we demonstrate the formation of kinetically trapped NCs assemblies with enhanced photoluminescence (PL) and excited state lifetimes and extend the principle to cluster impregnated cationic nanogels, nonluminescent Au(I)-thiolate complexes, and weakly luminescent CuNCs. We further demonstrate a thermal energy driven kinetic barrier breaking process to isolate these assemblies. These isolated assemblies are thermodynamically stable, built from a strong network among several discrete, ultrasmall AuNCs and exhibit several unusual properties such as high stability in various pH, strong PL, microsecond lifetimes, large Stocks shifts, and higher accumulation in the lysosome of cancer cells. We anticipate our strategy may find wider use in creating a large variety of MNC-based assemblies with many unforeseen arrangements, properties, and applications.

Polycationic Silver Nanoclusters Comprising Nanoreservoirs of Ag+ Ions with High Antimicrobial and Antibiofilm Activity.

Silver-based nano-antibiotics are rapidly developing as promising alternatives to conventional antibiotics. Ideally, to remain potent against a wide range of drug-resistant and anaerobic bacteria, silver-based nano-antibiotics should easily penetrate through the bacterial cell walls and actively release silver ions. In this study, highly monodispersed, ultrasmall (<3 nm), polycationic silver nanoclusters (pAgNCs) are designed and synthesized for the elimination of a range of common Gram-negative and Gram-positive pathogens and their corresponding established and matured biofilms, including those composed of multiple species. The pAgNCs also show greatly enhanced antibacterial efficacy against anaerobic bacteria such as Fusobacterium nucleatum and Streptococcus sanguinis. These results demonstrate that the cationic nature facilitates better penetration to the bacterial cell membrane while the presence of a high percentage (>50%) of silver ions (i.e., Ag+ nanoreservoirs) on the cluster surface maintains their efficiency in both aerobic and anaerobic conditions. Significantly, the pAgNCs showed a strong capacity to significantly delay the development of bacterial resistance when compared to similar-sized negatively charged silver nanoparticles or conventional antibiotics. This study demonstrates a novel design strategy that can lay the foundation for the development of future highly potent nano-antibiotics effective against a broad spectrum of pathogens and biofilms needed in many everyday life applications and industries.

Copper quantum clusters in protein matrix: potential sensor of Pb2+ ion.

A one-pot synthesis of extremely stable, water-soluble Cu quantum clusters (QCs) capped with a model protein, bovine serum albumin (BSA), is reported. From matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry, we assign the clusters to be composed of Cu(5) and Cu(13) cores. The QCs also show luminescence properties having excitation and emission maxima at 325 and 410 nm, respectively, with a quantum yield of 0.15, which are found to be different from that of protein alone in similar experimental conditions. The quenching of luminescence of the protein-capped Cu QCs in the presence of very low hydrogen peroxide concentration (approximately nanomolar, or less than part-per-billion) reflects the efficacy of the QCs as a potential sensing material in biological environments. Moreover, as-prepared Cu QCs can detect highly toxic Pb(2+) ions in water, even at the part-per-million level, without suffering any interference from other metal ions.

Driving Forces and Routes for Aggregation-Induced Emission-Based Highly Luminescent Metal Nanocluster Assembly.

The development of ultrasmall, luminescent metal nanoclusters (MNCs) with aggregation-induced emission (AIE) characteristics is a relatively new research area that has gained significant attention in various multidisciplinary applications such as optoelectronics, sensing, imaging, and therapy. The numerous scientific breakthroughs in the AIE field provide many tools that, if incorporated into MNCs design strategies, could help realize various new and exciting MNC-based avenues that maximize the utilization of the AIE phenomenon. Indeed, leveraging the aggregation strategies from the AIE community with the judicious use of various covalent and noncovalent interactions has been demonstrated to be effective for constructing several MNC-based hybrid assemblies with enhanced AIE characteristics. In this Perspective, we summarize the key driving forces and routes of MNC assembly together with their impact on deciphering the working mechanism behind the AIE process. These strategies can inspire the design of highly luminescent MNC-based hierarchical functional materials across multiple length scales.

Traceable Nanocluster-Prodrug Conjugate for Chemo-photodynamic Combinatorial Therapy of Non-small Cell Lung Cancer.

In cancer treatment, image-guided combinatorial therapy is usually a more promising approach than conventional therapy because it may overcome the drawbacks of conventional cancer treatment, such as tumor recurrence and multidrug resistance. To achieve a high therapeutic effect in image-guided combinatorial therapy, the therapeutic material should be traceable, biocompatible, and yet highly effective in eradicating tumors. For this purpose, we developed a traceable nanocarrier consisting of atomically precise gold nanoclusters (Au NCs, Au22(SG)18, abbreviated as Au22 NCs, where SG stands for glutathione) and a biopolymer (i.e., chitosan). This traceable nanocarrier (Chito-Au22) was then combined with dual prodrugs (i.e., chemotherapeutic platinum (Pt(IV)) prodrug and photodynamic aminolevulinic acid (ALA) prodrug) through a bioconjugation method. It was found that the final nanocomposite (abbreviated as Pt(IV)-ALA-Chito-Au22) has a pH-responsive drug release behavior, and the cumulative drug release can exceed 50% within 12 h at an acidic pH of 5.0. After 15 min of white light irradiation, the nanocomposite showed a synergistic killing effect on the A549 non-small cell lung carcinoma cell line. The Pt(IV)-ALA-Chito-Au22 nanocomposite also showed a high cellular uptake capacity and reactive oxygen species (ROS) generation capability, resulting in a significant killing effect on three-dimensional (3D) multicellular A549 spheroids. In the presence of light, the volume of the multicellular spheroids treated by our nanocomposites was reduced more than two times compared with those treated by a single prodrug/component. The nanocomposite also showed good cell viability on normal lung cell lines. The multifunctional nanocomposites developed in this study have broad prospects in both therapeutic and diagnostic applications.

Development and characterization of an oral microbiome transplant among Australians for the treatment of dental caries and periodontal disease: A study protocol.

BACKGROUND: Oral microbiome transplantation (OMT) is a novel concept of introducing health-associated oral microbiota into the oral cavity of a diseased patient. The premise is to reverse the state of oral dysbiosis, and restore the ecological balance to maintain a stable homeostasis with the host immune system. This study will assess the effectiveness, feasibility, and safety of OMT using an interdisciplinary approach. METHODS/DESIGN: To find donors suitable for microbial transplantation, supragingival plaque samples will be collected from 600 healthy participants. Each sample (200µL) will subsequently be examined in two ways: 1) 100µL of the sample will undergo high-throughput 16S rRNA gene amplicon sequencing and shotgun sequencing to identify the composition and characterisation of a healthy supragingival microbiome, 2) the remaining 100µL of the plaque sample will be mixed with 25% artificial saliva medium and inoculated into a specialised in-vitro flow cell model containing a hydroxyapatite disk. To obtain sufficient donor plaque, the samples would be grown for 14 days and further analysed microscopically and sequenced to examine and confirm the growth and survival of the microbiota. Samples with the healthiest microbiota would then be incorporated in a hydrogel delivery vehicle to enable transplantation of the donor oral microbiota. The third step would be to test the effectiveness of OMT in caries and periodontitis animal models for efficacy and safety for the treatment of oral diseases. DISCUSSION: If OMTs are found to be successful, it can form a new treatment method for common oral diseases such as dental caries and periodontitis. OMTs may have the potential to modulate the oral microbiota and shift the ecological imbalances to a healthier state.

Ultra-small gold nanoclusters assembled on plasma polymer-modified zeolites: a multifunctional nanohybrid with anti-haemorrhagic and anti-inflammatory properties.

Hemostatic agents are pivotal for managing clinical and traumatic bleeding during emergency and domestic circumstances. Herein, a novel functional hybrid nanocomposite material consisting of plasma polymer-modified zeolite 13X and ultra-small gold nanoclusters (AuNCs) was fabricated as an efficient hemostatic agent. The surface of zeolite 13X was functionalised with amine groups which served as binding sites for carboxylate terminated AuNCs. Protein corona studies revealed the enhanced adsorption of two proteins, namely, coagulation factors and plasminogen as a result of AuNCs immobilization on the zeolite surface. The immune response studies showed that the hybrid nanocomposites are effective in reducing inflammation, which combined with a greater attachment of vitronectin, may promote wound healing. The hemostatic potential of the nanocomposite could be directly correlated with their immunomodulatory and anti-haemorrhagic properties. Together, the hybrid nanoengineered material developed in this work could provide a new avenue to tackle life-threatening injuries in civilian and other emergencies.

The Impact of Engineered Silver Nanomaterials on the Immune System.

Over the last decades there has been a tremendous volume of research efforts focused on engineering silver-based (nano)materials. The interest in silver has been mostly driven by the element capacity to kill pathogenic bacteria. In this context, the main area of application has been medical devices that are at significant risk of becoming colonized by bacteria and subsequently infected. However, silver nanomaterials have been incorporated in a number of other commercial products which may or may not benefit from antibacterial protection. The rapid expansion of such products raises important questions about a possible adverse influence on human health. This review focuses on examining currently available literature and summarizing the current state of knowledge of the impact of silver (nano)materials on the immune system. The review also looks at various surface modification strategies used to generate silver-based nanomaterials and the immunomodulatory potential of these materials. It also highlights the immune response triggered by various silver-coated implantable devices and provides guidance and perspective towards engineering silver nanomaterials for modulating immunological consequences.