Synthesis,Chemical–Physical Characterization,and Biomedical Applications of Functional Gold Nanoparticles: A Review

Relevant properties of gold nanoparticles, such as stability and biocompatibility, together with their peculiar optical and electronic behavior, make them excellent candidates for medical and biological applications. This review describes the different approaches to the synthesis, surface modification, and characterization of gold nanoparticles (AuNPs) related to increasing their stability and available features useful for employment as drug delivery systems or in hyperthermia and photothermal therapy. The synthetic methods reported span from the well-known Turkevich synthesis, reduction with NaBH₄ with or without citrate, seeding growth, ascorbic acid-based, green synthesis, and Brust–Schiffrin methods. Furthermore, the nanosized functionalization of the AuNP surface brought about the formation of self-assembled monolayers through the employment of polymer coatings as capping agents covalently bonded to the nanoparticles. The most common chemical–physical characterization techniques to determine the size, shape and surface coverage of AuNPs are described underlining the structure–activity correlation in the frame of their applications in the biomedical and biotechnology sectors.     

Pharmacological Role of Functionalized Gold Nanoparticles in Disease Applications

Gold has always been regarded as a symbol of nobility, and its shiny golden appearance has always attracted the attention of many people. Gold has good ductility, molecular recognition properties, and good biocompatibility. At present, gold is being used in many fields. When gold particles are as small as several nanometers, their physical and chemical properties vary with their size in nanometers. The surface area of a nano-sized gold surface has a special effect. Therefore, gold nanoparticles can, directly and indirectly, give rise to different biological activities. For example, if the surface of the gold is sulfided. Various substances have a strong chemical reactivity and are easy to combine with sulfhydryl groups; hence, nanogold is often used in biomedical testing, disease diagnosis, and gene detection. Nanogold is easy to bind to proteins, such as antibodies, enzymes, or cytokines. In fact, scientists use nanogold to bind special antibodies, as a tool for targeting cancer cells. Gold nanoparticles are also directly cytotoxic to cancer cells. For diseases caused by inflammation and oxidative damage, gold nanoparticles also have antioxidant and anti-inflammatory effects. Based on these unique properties, gold nanoparticles have become the most widely studied metal nanomaterials. Many recent studies have further demonstrated that gold nanoparticles are beneficial for humans, due to their functional pharmacological properties in a variety of diseases. The content of this review will be the application of gold nanoparticles in treating or diagnosing pressing diseases, such as cancers, retinopathy, neurological diseases, skin disorders, bowel diseases, bone cartilage disorders, cardiovascular diseases, infections, and metabolic syndrome. Gold nanoparticles have shown very obvious therapeutic and application potential.     

A Review on Gold Nanotriangles: Synthesis,Self-Assembly and Their Applications

Gold nanoparticles (AuNPs) with interesting optical properties have attracted much attention in recent years. The synthesis and plasmonic properties of AuNPs with a controllable size and shape have been extensively investigated. Among these AuNPs, gold nanotriangles (AuNTs) exhibited unique optical and plasmonic properties due to their special triangular anisotropy. Indeed, AuNTs showed promising applications in optoelectronics, optical sensing, imaging and other fields. However, only few reviews about these applications have been reported. Herein, we comprehensively reviewed the synthesis and self-assembly of AuNTs and their applications in recent years. The preparation protocols of AuNTs are mainly categorized into chemical synthesis, biosynthesis and physical-stimulus-induced synthesis. The comparison between the advantages and disadvantages of various synthetic strategies are discussed. Furthermore, the specific surface modification of AuNTs and their self-assembly into different dimensional nano- or microstructures by various interparticle interactions are introduced. Based on the unique physical properties of AuNTs and their assemblies, the applications towards chemical biology and sensing were developed. Finally, the future development of AuNTs is prospected.     

金纳米粒子的细胞毒性

金纳米粒子(AuNPs)是构建用于诊断和治疗的纳米药物/探针的理想纳米材料之一,因此研究AuNPs与细胞的相互作用具有重要意义。 本文详细分析了金纳米簇(AuNCs)、球形金纳米粒子A(AuNPss)、金纳米球壳(AuNSs)和金纳米棒(AuNRs)等不同形貌的Au NPs对不同细胞模型的细胞毒性;讨论了AuNPs的理化性质(大小、形状、化学功能和表面电荷)对其细胞毒性的影响。 总结了AuNP细胞毒性研究遇到的挑战并提出相应解决方法。     

Anisotropic Gold Nanoparticles: Synthesis,Properties, Applications,and Toxicity

Anisotropic gold nanoparticles (AuNPs) have attracted the interest of scientists for over a century, but research in this field has considerably accelerated since 2000 with the synthesis of numerous 1D, 2D, and 3D shapes as well as hollow AuNP structures. The anisotropy of these nonspherical, hollow, and nanoshell AuNP structures is the source of the plasmon absorption in the visible region as well as in the near‐infrared (NIR) region. This NIR absorption is especially sensitive to the AuNP shape and medium and can be shifted towards the part of the NIR region in which living tissue shows minimum absorption. This has led to crucial applications in medical diagnostics and therapy (“theranostics”), especially with Au nanoshells, nanorods, hollow nanospheres, and nanocubes. In addition, Au nanowires (AuNWs) can be synthesized with longitudinal dimensions of several tens of micrometers and can serve as plasmon waveguides for sophisticated optical devices. The application of anisotropic AuNPs has rapidly spread to optical, biomedical, and catalytic areas. In this Review, a brief historical survey is given, followed by a summary of the synthetic modes, variety of shapes, applications, and toxicity issues of this fast‐growing class of nanomaterials.     

Gold Nanoparticles for Biology and Medicine

Gold colloids have fascinated scientists for over a century and are now heavily utilized in chemistry, biology, engineering, and medicine. Today these materials can be synthesized reproducibly, modified with seemingly limitless chemical functional groups, and, in certain cases, characterized with atomic‐level precision. This Review highlights recent advances in the synthesis, bioconjugation, and cellular uses of gold nanoconjugates. There are now many examples of highly sensitive and selective assays based upon gold nanoconjugates. In recent years, focus has turned to therapeutic possibilities for such materials. Structures which behave as gene‐regulating agents, drug carriers, imaging agents, and photoresponsive therapeutics have been developed and studied in the context of cells and many debilitating diseases. These structures are not simply chosen as alternatives to molecule‐based systems, but rather for their new physical and chemical properties, which confer substantive advantages in cellular and medical applications.     

Multifunctional Eco-Friendly Synthesis of ZnO Nanoparticles in Biomedical Applications

This work describes an environmental-friendly preparation of ZnO nanoparticles using aqueous oat extract. The advanced electrochemical and optical features of green synthesized ZnONPs displayed excellent antibacterial activity and exhibited an important role in pharmaceutical determinations. The formation of nanoscale ZnO was confirmed using various spectroscopic and microscopic investigations. The formed nanoparticles were found to be around 100 nm. The as-prepared ZnONPs were monitored for their antibacterial potential against different bacterial strains. The inhibition zones for ZnONPs were found as Escherichia coli (16 mm), Pseudomonas aeruginosa (17 mm), Staphylococcus aureus (12 mm) and Bacillus subtilis (11 mm) using a 30-µg mL⁻¹ sample concentration. In addition, ZnONPs exhibited significant antioxidant effects, from 58 to 67%, with an average IC₅₀ value of 0.88 ± 0.03 scavenging activity and from 53 to 71% (IC₅₀ value of 0.73 ± 0.05) versus the scavenging free radicals DPPH and ABTS, respectively. The photocatalytic potential of ZnONPs for Rhodamine B dye degradation under UV irradiation was calculated. The photodegradation process was carried out as a function of time-dependent and complete degradation (nearly 98%), with color removal after 120 min. Conclusively, the synthesized ZnONPs using oat biomass might provide a great promise in the future for biomedical applications.     

Green Synthesis of Gold Nanoparticles Using Plant Extracts as Beneficial Prospect for Cancer Theranostics

Gold nanoparticles (AuNPs) have been widely explored and are well-known for their medical applications. Chemical and physical synthesis methods are a way to make AuNPs. In any case, the hunt for other more ecologically friendly and cost-effective large-scale technologies, such as environmentally friendly biological processes known as green synthesis, has been gaining interest by worldwide researchers. The international focus on green nanotechnology research has resulted in various nanomaterials being used in environmentally and physiologically acceptable applications. Several advantages over conventional physical and chemical synthesis (simple, one-step approach to synthesize, cost-effectiveness, energy efficiency, and biocompatibility) have drawn scientists’ attention to exploring the green synthesis of AuNPs by exploiting plants’ secondary metabolites. Biogenic approaches, mainly the plant-based synthesis of metal nanoparticles, have been chosen as the ideal strategy due to their environmental and in vivo safety, as well as their ease of synthesis. In this review, we reviewed the use of green synthesized AuNPs in the treatment of cancer by utilizing phytochemicals found in plant extracts. This article reviews plant-based methods for producing AuNPs, characterization methods of synthesized AuNPs, and discusses their physiochemical properties. This study also discusses recent breakthroughs and achievements in using green synthesized AuNPs in cancer treatment and different mechanisms of action, such as reactive oxygen species (ROS), mediated mitochondrial dysfunction and caspase activation, leading to apoptosis, etc., for their anticancer and cytotoxic effects. Understanding the mechanisms underlying AuNPs therapeutic efficacy will aid in developing personalized medicines and treatments for cancer as a potential cancer therapeutic strategy.     

甲烷氧化菌素催化纳米金合成

甲烷氧化菌素(methanobactin,mb)是具有过氧化氢还原酶活性的荧光肽.从甲基弯菌Methylosinus trichospo-rium IMV3011限铜培养介质中分离mb,采用紫外可见全波长扫描法观察mb催化对苯二酚还原氯金酸合成纳米金的作用和影响,当mb/氯金酸/对苯二酚反应液中mb的浓度分别是2.5×10-5mol/L、5.0×10-5mol/L和1.0×10-4mol/L时,形成的纳米金溶液的特征峰分别是561.5 nm(OD561=0.158)、548.0 nm(OD5 48=0.426)、536.5 nm(OD5 36=0.541),特征峰波长减小,对应的吸光值增大,表明mb能够催化对苯二酚还原氯金酸合成纳米金,并且可以通过调控mb的浓度控制纳米金的合成量及粒径大小.     

Green Silver and Gold Nanoparticles: Biological Synthesis Approaches and Potentials for Biomedical Applications

The nanomaterial industry generates gigantic quantities of metal-based nanomaterials for various technological and biomedical applications; however, concomitantly, it places a massive burden on the environment by utilizing toxic chemicals for the production process and leaving hazardous waste materials behind. Moreover, the employed, often unpleasant chemicals can affect the biocompatibility of the generated particles and severely restrict their application possibilities. On these grounds, green synthetic approaches have emerged, offering eco-friendly, sustainable, nature-derived alternative production methods, thus attenuating the ecological footprint of the nanomaterial industry. In the last decade, a plethora of biological materials has been tested to probe their suitability for nanomaterial synthesis. Although most of these approaches were successful, a large body of evidence indicates that the green material or entity used for the production would substantially define the physical and chemical properties and as a consequence, the biological activities of the obtained nanomaterials. The present review provides a comprehensive collection of the most recent green methodologies, surveys the major nanoparticle characterization techniques and screens the effects triggered by the obtained nanomaterials in various living systems to give an impression on the biomedical potential of green synthesized silver and gold nanoparticles.     

A Simple Protocol to Stabilize Gold Nanoparticles using Amphiphilic Block Copolymers: Stability Studies and Viable Cellular Uptake

Di‐ and triblock non‐ionic copolymers based on poly(ethylene oxide) and poly(propylene oxide) were studied for the stabilization of nanoparticles in water at high ionic strength. The effect of the molecular architecture (di‐ vs. triblock) of these amphiphilic copolymers was investigated by using gold nanoparticles (AuNPs) as probes for colloidal stability. The results demonstrate that both di‐ and triblock copolymers can provide long term stability, and that in both cases AuNPs are individually embedded within globules of polymers. However, in the case of diblock copolymers, the colloidal stability was related to the formation of micelles, in contrast with the case of triblock copolymers, which were previously shown to provide good stability even at concentrations at which micelles do not form. Quartz crystal microbalance (QCM) experiments showed that the presence of the hydrophobic block in the structure of the polymer is important to ensure quantitative adsorption upon a gold surface and to limit desorption. We demonstrate that with an appropriate choice of polymer, the polymer/AuNP hybrids can also undergo filtration and freeze‐drying without noticeable aggregation, which can be very convenient for further applications. Finally, preliminary studies of the cytotoxicity effect on fibroblast cells show that the polymer/AuNP hybrids were not cytotoxic. TEM micrographs on ultrathin sections of cells after incubation with the colloidal solutions show that the nanoparticles were internalized into the cells, conserving their initial size and shape.     

Bisthiol-Assisted Multilayers' Self-Assembly of Gold Nanoparticles: Synthesis,Characterization, Size Control and Electrocatalytic Applications

The layer-by-layer (LBL) approach has been utilized to self-assemble multilayers films of citrate-stabilized gold nanoparticles (AuNPs) on polycrystalline gold (poly-Au) substrates. 1,4-benzenedimethanethiol (BDMT) was used as a cross linker to bind every two successive AuNPs layers. The transmission electron microscopy (TEM), and X-ray photoelectron spectroscopy (XPS) techniques were employed to confirm the existence of the alternative layers of AuNPs and BDMT in the self-assembled multilayers film. The AuNPs modified poly-Au electrode showed a significant electrocatalysis towards the reduction of oxygen (a positive potential shift of about 100 mV was observed in the reduction peak potential compared to that obtained at the bare poly-Au electrode). The AuNPs tend to aggregate during their assembling to different extent which markedly depends on the substrate geometry and roughness. An effort was dedicated to understand and control the aggregation phenomenon.     

Phytochemical Profile,Antimicrobial, Cytotoxic,and Antioxidant Activities of Fresh and Air-Dried Satureja nabateorum Essential Oils

Satureja nabateorum (Danin and Hedge) Bräuchler is a perennial herb in the Lamiaceae family that was discovered and classified in 1998. This green herb is restricted to the mountains overlooking the Dead Sea, specifically in Jordan’s southwest, the Edom mountains, and the Tubas mountains in Palestine. Gas chromatography-mass spectrometry (GC-MS) analysis of essential oil (EO) of air-dried and fresh S. nabateorum resulted in the identification of 30 and 42 phytochemicals accounting for 99.56 and 98.64% of the EO, respectively. Thymol (46.07 ± 1.1 and 40.64 ± 1.21%) was the major compound, followed by its biosynthetic precursors γ-terpinene (21.15 ± 1.05% and 20.65 ± 1.12%), and p-cymene (15.02 ± 1.02% and 11.51 ± 0.97%), respectively. Microdilution assay was used to evaluate the antimicrobial property of EOs against Staphylococcus aureus (ATCC 25923), clinical isolate Methicillin-Resistant Staphylococcus aureus (MRSA), Enterococcus faecium (ATCC 700221) Klebsiella pneumoniae (ATCC 13883), Proteus vulgaris (ATCC 700221), Escherichia coli (ATCC 25922) and Pseudomonas aeruginosa (ATCC 27853) and Candida albicans (ATCC-90028). With a MIC of 0.135 μg/mL, the EOs has the most potent antibacterial action against K. pneumonia. Both EOs display good antifungal efficacy against C. albicans, with a MIC value of 0.75 μg/mL, which was better than that of Fluconazole’s (positive control, MIC = 1.56 μg/mL). The antioxidant capacity of EOs extracted from air-dried and fresh S. nabateorum was determined using the DPPH assay, with IC₅₀ values of 4.78 ± 0.41 and 5.37 ± 0.40 μg/mL, respectively. The tested EOs showed significant cytotoxicity against Hela, HepG2, and COLO-205 cells, with IC₅₀ values ranging from 82 ± 0.98 to 256 ± 1.95 μg/mL. The current work shows there is a possibility to use the S. nabateorum EOs for various applications.     

Dendronized Gelatin-Mediated Synthesis of Gold Nanoparticles

Thermoresponsive dendronized gelatins (GelG1) or gelatin methacrylates (GelG1MA) were used as precursors to modulate the efficient reduction of Au(III) to form stable gold nanoparticles (AuNPs) through UV irradiation. These dendronized gelatins were obtained through the amidation of gelatin or gelatin methacrylates with dendritic oligoethylene glycols (OEGs). Crowded OEG dendrons along the gelatin backbones create a hydrophobic microenvironment, which promotes the reduction of Au(III). Gelatin backbones act as ligands through the electron-rich groups to facilitate the reduction, while the dendritic OEGs provide shielding effects through crowding to form a hydrophobic microenvironment, which not only enhances the reduction but also stabilize the formed AuNPs through encapsulation. The effects of dendron coverage on the dendronized biomacromolecules and their thermoresponsiveness on the reduction kinetics were examined. Dendronized gelatin/AuNPs hydrogels were further prepared through the in situ photo-crosslinking of GelG1MA. The modification of natural macromolecules through dendronization presented in this report facilitates a novel platform for the environmentally friendly synthesis of noble metal nanoparticles, which may form a new strategy for developing smart nano-biosensors and nano-devices.     

A Cytotoxic Bis(1,2,3-triazol-5-ylidene)carbazolide Gold(III) Complex Targets DNA by Partial Intercalation

The syntheses of bis(triazolium)carbazole precursors and their corresponding coinage metal (Au, Ag) complexes are reported. For alkylated triazolium salts, di- or tetranuclear complexes with bridging ligands were isolated, while the bis(aryl) analogue afforded a bis(carbene) Au^I-CNC pincer complex suitable for oxidation to the redox-stable [Au^III(CNC)Cl]⁺ cation. Although the ligand salt and the [Au^III(CNC)Cl]⁺ complex were both notably cytotoxic toward the breast cancer cell line MDA-MB-231, the Au^III complex was somewhat more selective. Electrophoresis, viscometry, UV-vis, CD and LD spectroscopy suggest the cytotoxic [Au^III(CNC)Cl]⁺ complex behaves as a partial DNA intercalator. In silico screening indicated that the [Au^III(CNC)Cl]⁺ complex can target DNA three-way junctions with good specificity, several other regular B-DNA forms, and Z-DNA. Multiple hydrophobic π-type interactions involving T and A bases appear to be important for B-form DNA binding, while phosphate O⋅⋅⋅Au interactions evidently underpin Z-DNA binding. The CNC ligand effectively stabilizes the Au^III ion, preventing reduction in the presence of glutathione. Both the redox stability and DNA affinity of the hit compound might be key factors underpinning its cytotoxicity in vitro.     

Recent Advances in Inorganic Nanomaterials Synthesis Using Sonochemistry: A Comprehensive Review on Iron Oxide,Gold and Iron Oxide Coated Gold Nanoparticles

Sonochemistry uses ultrasound to improve or modify chemical reactions. Sonochemistry occurs when the ultrasound causes chemical effects on the reaction system, such as the formation of free radicals, that intensify the reaction. Many studies have investigated the synthesis of nanomaterials by the sonochemical method, but there is still very limited information on the detailed characterization of these physicochemical and morphological nanoparticles. In this comprehensive review, recent advances in the sonochemical synthesis of nanomaterials based on iron oxide nanoparticles (Fe₃O₄NP), gold nanoparticles (AuNP) and iron oxide-coated gold nanoparticles (Fe₃O₄@Au NP) are discussed. These materials are the most studied materials for various applications, such as medical and commercial uses. This review will: (1) address the simple processing and observations on the principles of sonochemistry as a starting point for understanding the fundamental mechanisms, (2) summarize and review the most relevant publications and (3) describe the typical shape of the products provided in sonochemistry. All in all, this review’s main outcome will provide a comprehensive overview of the available literature knowledge that promotes and encourages future sonochemical work.     

Nanotechnology,Green Synthesis and Biological Activity Application of Zinc Oxide Nanoparticles Incorporated Argemone Mxicana Leaf Extract

Nanomaterial is a rapidly growing area that is used to create a variety of new materials and nanotechnology applications from medical, pharmaceuticals, chemical, mechanical, electronics and several environmental industries including physical, chemical and biological nanoparticles are very important in our daily life. Nanoparticles with leaf extract from the healthy plant are important in the area of research using biosynthesis methods. Because of it’s used as an environmentally ecofriendly, other than traditional physical and chemical strategies. In particular, biologically synthesized nanoparticles have become a key branch of nanotechnology. The present work presents a synthesis of zinc oxide nanoparticles using an extract from the Argemone leaf Mexicana. Biosynthetic nanoparticles are characterized by X-ray diffraction (XRD), Ultraviolet visible (UV-vis) spectroscopy analysis, a Fourier Transform Infrared Spectroscopy analysis (FTIR) and a scanning electron microcopy (SEM), X-ray analysis with dispersive energy (EDAX). XRD is used to examine the crystalline size of zinc oxide nanoparticles. The FTIR test consists in providing evidence of the presence of targeted teams. UV is used for optical properties and calculates the energy of the bandwidth slot. The scanning microscope emission reveals the morphology of the surface and the energy dispersive X-ray analysis confirms the basic composition of zinc oxide nanoparticles. It is found that zinc nanoparticles are capable of achieving high anti-fungal efficacy and therefore have a high potential antimicrobial activity of ZnO NPs, like antibacterial and high antioxidant. Zinc Oxide nanoparticles from the Argemone Mexicana leaf extract have several antimicrobial applications, such as medical specialty, cosmetics, food, biotechnology, nano medicine and drug delivery system. ZnO nanoparticles are important because they provide many practical applications in industry. The most important use of nanoparticles of ZnO would be strong antibacterial and antioxidant activity with a simple and efficient biosynthesis method may be used for future work applications.     

Fluorescent Gold Nanoparticles: Synthesis of Composite Materials of Two‐Component Disulfide Gels and Gold Nanoparticles

Pseudoenantiomeric ethynylhelicene oligomers containing a disulfide group formed two‐component gels, which showed different solvent properties from gels without the disulfide group. The disulfide gels reacted with gold nanoparticles, and the resulting organic–inorganic composite materials exhibited fluorescence emission between 600–800 nm, along with emission from the oligomers at 450 nm. The disulfide gels and isolated gold nanoparticles loaded with the oligomers did not show the former emission. The 600–800 nm emission reversibly disappeared upon sol formation with heating, which was accompanied by an enhancement of the emission at 450 nm. The novel emission was also observed in the solid state.     

Nonfunctionalized Gold Nanoparticles: Synthetic Routes and Synthesis Condition Dependence

Since Faraday first described gold sol synthesis, synthetic routes to nanoparticles, as well as their applications, have experienced a huge growth. Variations in synthesis conditions such as pH, temperature, reduction, and the stabilizing agent used will determine the morphology, size, monodispersity, and stability of nanoparticles obtained, allowing for modulation of their physical and chemical properties. Although many studies have been made about the synthesis and characterization of individual nanosystems of interest, to our knowledge the common, general traits that all those synthesis share have not been previously compiled. In this review, we aim to offer a global vision of some of the most relevant synthetic procedures reported up to date, with a special focus on nonfunctionalized gold nanoparticle synthetic routes in aqueous media, and to display a broad overview of the influence that synthesis conditions have on the shape, stability, and reactivity of nanoparticle systems.     

Synthesis and Characterization of Thiophene‐derived Amido Bis‐nitrogen Mustard and Its Antimicrobial and Anticancer Activities

The thiophene‐derived amido bis‐nitrogen mustard N²,N²,N⁵,N⁵‐tetrakis(2‐chloroethyl)‐3,4‐dimethylthiophene‐2,5‐dicarboxamide was designed and synthesized via five‐step reactions from commercially available 2‐chloroacetonitrile. This target compound was confirmed by ¹H NMR, ¹³C NMR, MS, IR spectra and elemental analyses, and its structure was further characterized by X‐ray single‐crystal analysis. The biological activities for the title compound and some intermediates were evaluated in vitro for their antibacterial, antifungal and cytotoxic activities. The preliminary results showed that the title compound could inhibit efficiently the growth of the tested microorganisms including drug‐resistant bacteria MRSA to some extent. Moreover, the target compound was found to be effective against prostatic carcinoma cell line (PC‐3), breast carcinoma cell line (MCF‐7), colon carcinoma (LoVo) and lung cancer (A549). Especially, it gave selective antitumor efficacy against prostatic carcinoma cell line (PC‐3) at a low dose.