Glutamic Acid Modified Gold Nanorod Sensor for the Detection of Calcium ions in Neuronal Cells.

Calcium (Ca2+) ions play a crucial role in the functioning of neurons, governing various aspects of neuronal activity such as rapid modulation and alterations in gene expression. Ca2+ signaling has a significant impact on the development of diseases and the impairment of neuronal functions. Herein, the study reports a Ca2+ ion sensor in neuronal cells using a gold nanorod. The gold nanorod (GA-GNR) conjugated glutamic acid developed in the study was used as a nano-bio probe for the experimental and in vitro detection of calcium. The nanosensor is colloidally stable, preserves plasmonic properties, and shows good viability in neuronal cells, as well as promoting neuron cell line growth. The cytotoxicity and cell penetration of the nanosensor are studied using Raman spectroscopy, brightfield and darkfield microscopy imaging, and MTT assays. The quantification of Ca2+ ions in neuronal cells is determined by monitoring the surface plasmon resonance (SPR) of the GA-GNR. The change in the intensity profile in the presence of Ca2+ incubated neurons was effectively used to develop a portable prototype of an optical Ca2+ sensor, proposing it as a tool for neurodegenerative disease diagnosis and neuromodulation evaluation.

Porphyrin and doxorubicin mediated nanoarchitectonics of copper clusters: a bimodal theranostics for cancer diagnosis and treatment in vitro.

Nanoarchitectonics, an emerging strategy, presents a promising alternative for developing highly efficient next-generation functional materials. Multifunctional materials developed using nanoarchitectonics help to mimic biological molecules. Porphyrin-based molecules can be effectively utilized to design such assemblies. Metal nanocluster is one of the functional materials that can shed more insight into developing nanoarchitectonic materials. Herein, an inherently near-infrared (NIR) fluorescing copper nanocluster (CuC)-mediated structural assembly via protoporphyrin IX (PPIX) and doxorubicin (Dox) is demonstrated as the functional material. Dox-loaded porphyrin-mediated CuC assembly shows singlet oxygen generation and 66% drug release at 15 min. Furthermore, the efficacy of this material is tested for cancer diagnosis and bimodal therapeutic strategy due to the fluorescing ability of the cluster and loading of PPIX as well as the drug, respectively. The nanoarchitecture exhibits targeted imaging and 83% cell death in HeLa cells upon laser irradiation with 10 nmoles and 20 nmoles of PPIX and Dox, respectively.

Correction: An insight into the optical properties of a sub nanosize glutathione stabilized gold cluster.

Correction for 'An insight into the optical properties of a sub nanosize glutathione stabilized gold cluster' by Lakshmi V. Nair et al., Dalton Trans., 2016, 45, 11286-11291, https://doi.org/10.1039/C6DT01753C.

A nanoarchitecture of a gold cluster conjugated gold nanorod hybrid system and its application in fluorescence imaging and plasmonic photothermal therapy.

Engineering different nanomaterials into a single functional material can impart unique properties of the parental nanoparticles, especially in the field of bio imaging and therapy. Gold nanomaterials having different sizes, shapes and dimensionalities exhibit exceptional properties apart from their non-toxicity and hence are strong candidates in the biomedical field. Designing a hybrid nanomaterial of two gold nanostructures retaining the individual properties of the parental nanomaterials is challenging. Here, we demonstrate the synthesis of a hybrid nanomaterial (GQC@GNR), comprising an extremely small gold nanocluster and a representative of the asymmetric gold nanostructure, i.e., a gold nanorod, both having their own different exclusive optical properties like tuneable emission and NIR absorption characteristics, respectively. The hybrid system is designed to retain its emission and absorption in the NIR region to use it as an agent for simultaneous imaging and therapy. The formation of GQC@GNR and its architectonics heavily depend on the synthesis route and the parameters adopted which in turn have a direct influence on its properties. The architecture and its connection to the optical properties are explained using UV-Vis absorption and photoluminescence spectroscopy, zeta potential, transmission electron microscopy, etc. DFT-based computational modelling supports architectonics as explained by the experimental findings. The formation of the gold-gold hybrid system witnessed interesting science with a strong indication that materials with desired properties can be designed by appropriately modulating the architectonics of hybrid formation. Finally, folate conjugated GQC@GNR demonstrated its efficacy for targeted imaging and photothermal therapy in HeLa cells and tumor-bearing animal models. The detailed therapeutic efficacy of GQC@GNR is also explained based on Raman spectroscopy.

Copper Nanocluster Enables Simultaneous Photodynamic and Chemo Therapy for Effective Cancer Diagnosis and Treatment in Vitro.

Metal-nanocluster-mediated cancer diagnosis and therapy has drawn considerable attention in recent years due to the unique optical and photophysical properties of metal clusters. This type of material is highly useful for the diagnosis, treatment, and further follow-up of disease. However, a single treatment modality is not sufficient for a complete cure. The use of a multi-therapeutic strategy is among the most promising methods for effective treatment, along with an early-stage diagnosis. To address the multiple therapeutic modalities in a single nanomaterial, a copper nanocluster was synthesized using glutathione, having inherent singlet oxygen generation and emission at 674 nm. A tumor-targeting agent (folic acid) and an anticancer drug (doxorubicin) was conjugated to the copper cluster for cancer diagnosis via targeted imaging and further double therapy (photodynamic and chemotherapy) in vitro. 10.5 µg (18.1 nmol) of drug conjugated copper cluster shows 56 % cell death for 30 second laser irradiation in HeLa cells. Effective cancer cell imaging and therapeutic efficacy are demonstrated in vitro.

Gold nanoclusters as electrocatalysts: size, ligands, heteroatom doping, and charge dependences.

To establish an ultimate energy conversion system consisting of a water-splitting photocatalyst and a fuel cell, it is necessary to further increase the efficiencies of the hydrogen evolution reaction (HER), the oxygen evolution reaction (OER), and the oxygen reduction reaction (ORR). Recently, it was demonstrated that thiolate (SR)-protected gold clusters, Aun(SR)m, and their related alloy clusters can serve as model catalysts for these three reactions. However, as the previous data have been obtained under different experimental conditions, it is difficult to use them to gain a deep understanding of the means to attain higher activity in these reactions. Herein, we measured the HER, OER, and ORR activities of Aun(SR)m and alloy clusters containing different numbers of constituent atoms, ligand functional groups, and heteroatom species under identical experimental conditions. We obtained a comprehensive set of results that illustrates the effect of each parameter on the activities of the three reactions. Comparison of the series of results revealed that decreasing the number of constituent atoms in the cluster, decreasing the thickness of the ligand layer, and substituting Au with Pd improve the activities in all reactions. Taking the stability of the cluster into consideration, [Au24Pd(PET)18]0 (PET = 2-phenylethanethiolate) can be considered as a metal cluster with high potential as an HER, OER, and ORR catalyst. These findings are expected to provide clear design guidelines for the development of highly active HER, OER, and ORR catalysts using Aun(SR)m and related alloy clusters, which would allow realization of an ultimate energy conversion system.

Luminescent Gold Nanorods To Enhance the Near-Infrared Emission of a Photosensitizer for Targeted Cancer Imaging and Dual Therapy: Experimental and Theoretical Approach.

Strong plasmon absorption in the near-infrared (NIR) region renders gold nanorods (GNRs) amenable for biomedical applications, particularly for photothermal therapy. However, these nanostructures have not been explored for their imaging potential because of their weak emission profile. In this study, the weak fluorescence emission of GNRs is tuned to match that of the absorption of a photosensitizer (PS) molecule, and energy transfer from the GNR to PS enhances the emission profile of the GNR-PS combination. GNR complexes generally quench the fluorescence emission of nearby chromophores. However, herein, the complex retains or rather enhances the fluorescence through competition in energy transfer. Excitation-dependent energy transfer has been explained experimentally and theoretically by using DFT calculations, the CIE chromaticity diagram, and power spectrum. The final GNR-PS complex modified for tumor specificity serves as an excellent organ-specific theranostic probe for bioimaging and dual therapy both in vitro and in vivo. Principal component analysis designates photodynamic therapy a better candidate than that of photothermal therapy for long-term efficacy in vivo.

Genetic characterization reveals evidence for an association between water contamination and zoonotic transmission of a Cryptosporidium sp. from dairy cattle in West Bengal, India.

Cryptosporidium sp. is an enteric parasite with zoonotic potential, and can infect a wide range of vertebrates, including human. Determining the source of infection and the mode of transmission in a new endemic region is crucial for the control of cryptosporidiosis. In the present study, we have assessed the importance of dairy cattle as a potential source of Cryptosporidium infection for humans in a newly recognized endemic region. Cryptosporidium isolates from dairy calves, humans (farm workers) and nearby water bodies were genetically characterized based on 18SrRNA and hsp70 genes. A high incidence of Cryptosporidium infection was identified in our study region. This finding is of public health concern. Cryptosporidium ryanae rather than Cryptosporidium parvum has been identified as the most prevalent infecting species in the study region. Infections were associated with clinical symptoms of infected animals. An incomplete linkage disequilibrium (LD) value with potential recombination events at 18SrRNA locus were identified for the first time in C. ryanae, which was previously reported as a clonal population. Phylogenetic analysis revealed the presence of identical genotypes of a Cryptosporidium sp. from dairy calves, farm workers and nearby water bodies and indicates an association between water contamination and zoonotic transmission of Cryptosporidiosis in our study region.

Alloy Clusters: Precise Synthesis and Mixing Effects.

Metal alloys exhibit functionalities unlike those of single metals. Such alloying has drawn considerable research interest, particularly for nanoscale particles (metal clusters/nanoparticles), from the viewpoint of creating new functional nanomaterials. In gas phase cluster research, generated alloy clusters can be spatially separated with atomic precision in vacuum. Thus, the influences of increases or decreases in each element on the overall electronic structure of the cluster can be elucidated. However, to further understand the related mixing and synergistic effects, alloy clusters need to be produced on a large scale and characterized by various techniques. Because alloy clusters protected by thiolate (SR) can be synthesized by chemical methods and are stable in both solution and the solid state, these clusters are ideal study materials to better understand the mixing and synergistic effects. Moreover, the alloy clusters thus created have potential applications as functional materials. Therefore, since 2008, we have been working on establishing a precise synthesis method for SR-protected alloy clusters and elucidating their mixing and synergistic effects. Early research focused on the precise synthesis of alloy clusters wherein some of the Au in the stable SR-protected gold clusters ([Au25(SR)18]- and [Au38(SR)24]0) is replaced by Pd, Ag, or Cu. These studies have shown that Pd, Ag, or Cu substitute at different metal sites. We also have examined the as-synthesized alloy clusters to clarify the effect of substitution by each element on the physical and chemical properties of the clusters. However, in early studies, the number of substitutions could not be controlled with atomic accuracy for [Au25- xM x(SR)18]- (M = Ag or Cu). Then, in following research, methods have been established to obtain alloy clusters with control over the composition. We have succeeded in developing a method for controlling the number of Ag substitutions with atomic precision and thereby elucidating the effect of Ag substitution on the electronic structure of clusters with atomic precision. Concurrently, we also studied alloy clusters containing multiple heteroelements with different preferential substitution sites. These results revealed that the effects of substitution of each element can be superimposed on the cluster by combining multiple elemental substitutions at different sites. In addition, we successfully developed methods to synthesize alloy clusters with heterometal core. These findings are expected to lead to clear design guidelines for developing new functional nanomaterials.

Hetero-biicosahedral [Au24Pd(PPh3)10(SC2H4Ph)5Cl2]+ nanocluster: selective synthesis and optical and electrochemical properties.

A recent study implied that a hetero-biicosahedral 25-atom cluster composed of two kinds of icosahedral 13-atom clusters could serve as a molecular rectifier and dipole material. However, no hetero-biicosahedral 25-atom clusters containing three types of ligands, in this case, phosphines, halogens, and thiolates, have been reported. In this study, we selectively synthesized [Au24Pd(PPh3)10(SC2H4Ph)5Cl2]Cl (Au = gold, Pd = palladium, PPh3 = triphenylphosphine, SC2H4Ph = phenylethanethiolate, Cl = chloride), in which one Au was replaced with a Pd. The single-crystal X-ray structural analysis demonstrated that [Au24Pd(PPh3)10(SC2H4Ph)5Cl2]Cl was a hetero-biicosahedral 25-atom cluster in which the central atom of one icosahedral Au13 core was replaced by a Pd atom. Optical absorption spectroscopy suggested that the electronic structure of each individual icosahedral 13-atom core in [Au24Pd(PPh3)10(SC2H4Ph)5Cl2]+ was reasonably well maintained, similar to the case of [Au25(PPh3)10(SC2H4Ph)5Cl2]2+. Density functional theory calculation revealed that the peak splitting in the region below 2.2 eV of the optical absorption spectrum of [Au24Pd(PPh3)10(SC2H4Ph)5Cl2]+ is due to the splitting of HOMOs and also suggested that this cluster has dipole moment. Electrochemical measurements showed that [Au24Pd(PPh3)10(SC2H4Ph)5Cl2]+ was relatively stable to reduction. These results are expected to contribute to the development of molecular rectifiers and dipole materials based on hetero-biicosahedral 25-atom clusters.

Atomic and Isomeric Separation of Thiolate-Protected Alloy Clusters.

Techniques to control the chemical compositions and geometric structures of alloy clusters are indispensable to understand the correlation between the structures and physical/chemical properties of alloy clusters. In this study, we established a method to separate thiolate-protected 25-atom gold-silver alloy clusters (Au25- xAg x(SR)18) according to their chemical composition and structural isomer. Furthermore, using this method, we revealed that an isomeric distribution of the products exists in Au25- xAg x(SR)18 ( x ≥ 2) and that the distribution of these isomers depends on the synthesis method and standing time in solution. In this study, it was also demonstrated that the continuous discretization of the electronic structure is induced by the Ag substitution. This method can also be used to separate mixtures of [Au24M(SR)18]0 (M = Au, Pt, or Pd) and other Au-Ag alloy clusters ([Au36- xAg x(SR)24]0 and [Au38- xAg x(SR)24]0). This method is expected to be used to obtain comprehensive knowledge of the structural-property correlation of alloy clusters.

Thiolate-Protected Trimetallic Au∼20Ag∼4Pd and Au∼20Ag∼4Pt Alloy Clusters with Controlled Chemical Composition and Metal Positions.

The mixing of heteroelements in metal clusters is a powerful approach to generate new physical/chemical properties and functions. However, as the kinds of elements increase, control of the chemical composition and geometric structure becomes difficult. We succeeded in the compositionally selective synthesis of phenylethanethiolate-protected trimetallic Au∼20Ag∼4Pd and Au∼20Ag∼4Pt clusters, Au∼20Ag∼4Pd(SC2H4Ph)18 and Au∼20Ag∼4Pt(SC2H4Ph)18. Single-crystal X-ray structural analysis revealed the precise position of each metal element in these metal clusters. Reacting with thiol at an elevated temperature was found to be important to direct the metal elements to the most stable positions. The electronic structures of these trimetallic clusters become more discretized than those of the related bimetallic clusters due to orbital splitting.

High-performance liquid chromatography mass spectrometry of gold and alloy clusters protected by hydrophilic thiolates.

In this work, we found two hydrophilic interaction liquid chromatography (HILIC) columns for high-performance liquid chromatography (HPLC) suitable for the high-resolution separation of hydrophilic metal clusters. The mass distributions of the product mixtures of hydrophilic metal clusters were evaluated via HPLC mass spectrometry (LC/MS) using these HILIC columns. Consequently, we observed multiple clusters that had not been previously reported for glutathionate (SG)-protected gold clusters (Aun(SG)m). Additionally, we demonstrated that Aun-xMx(SG)m alloy clusters (M = Ag, Cu, or Pd) in which part of the Au in the Aun(SG)m cluster is replaced by a heteroelement can be synthesized, similar to the case of hydrophobic alloy clusters. It is easy to evaluate the mass distributions of hydrophilic metal clusters using this method. Thus, remarkable progress in the synthesis techniques of hydrophilic metal clusters through the use of this method is anticipated, as is the situation for hydrophobic metal clusters.

An insight into the optical properties of a sub nanosize glutathione stabilized gold cluster.

In this study, gold quantum clusters with distinct fluorescence properties were developed and their structural and physical behaviour was evaluated. The clusters were prepared by etching gold nanoparticles with glutathione. Three different Au33 clusters with emission profiles in the NIR region and one blue emitting cluster, Au8 were developed by varying the geometrical arrangement of atoms within the cluster. These clusters having sizes in the range of 0.7 to 2 nm were synthesized by choosing different reaction temperatures from 0 °C to 70 °C and pH between 1.5 and 10. In the three cases, formation of self assembled atoms within the cluster and the corresponding changes in optical properties were observed. A detailed evaluation of the number of atoms and the core-ligand ratio using MALDI-MS and a change in the binding energy as seen in the XPS study confirmed this finding. The study demonstrates that the self assembly of atoms and their arrangement is an important factor in determining the characteristics of the cluster. In this communication, we put forward a new concept where the number of atoms and their arrangement within the clusters play a crucial role in tuning their optical properties.

Investigation of apoptotic events at molecular level induced by SERS guided targeted theranostic nanoprobe.

Herein, we have examined distinctive structural and functional variations of cellular components during apoptotic cell death induced by a targeted theranostic nanoprobe, MMP-SQ@GNR@LAH-DOX, which acted as a SERS "on/off" probe in the presence of a MMP protease and executed synergistic photothermal chemotherapy, as reflected by the SERS fingerprinting, corresponding to the phosphodiester backbone of DNA.

Fluorescence Imaging Assisted Photodynamic Therapy Using Photosensitizer-Linked Gold Quantum Clusters.

Fluorescence imaging assisted photodynamic therapy (PDT) is a viable two-in-one clinical tool for cancer treatment and follow-up. While the surface plasmon effect of gold nanorods and nanoparticles has been effective for cancer therapy, their emission properties when compared to gold nanoclusters are weak for fluorescence imaging guided PDT. In order to address the above issues, we have synthesized a near-infrared-emitting gold quantum cluster capped with lipoic acid (L-AuC with (Au)18(L)14) based nanoplatform with excellent tumor reduction property by incorporating a tumor-targeting agent (folic acid) and a photosensitizer (protoporphyrin IX), for selective PDT. The synthesized quantum cluster based photosensitizer PFL-AuC showed 80% triplet quantum yield when compared to that of the photosensitizer alone (63%). PFL-AuC having 60 µg (0.136 mM) of protoporphyrin IX was sufficient to kill 50% of the tumor cell population. Effective destruction of tumor cells was evident from the histopathology and fluorescence imaging, which confirm the in vivo PDT efficacy of PFL-AuC.

Quantum dot tailored to single wall carbon nanotubes: a multifunctional hybrid nanoconstruct for cellular imaging and targeted photothermal therapy.

Hybrid nanomaterial based on quantum dots and SWCNTs is used for cellular imaging and photothermal therapy. Furthermore, the ligand conjugated hybrid system (FaQd@CNT) enables selective targeting in cancer cells. The imaging capability of quantum dots and the therapeutic potential of SWCNT are available in a single system with cancer targeting property. Heat generated by the system is found to be high enough to destroy cancer cells.