Zebrafish Insights into Nanomaterial Toxicity: A Focused Exploration on Metallic, Metal Oxide, Semiconductor, and Mixed-Metal Nanoparticles.

Nanomaterials are widely used in various fields, and ongoing research is focused on developing safe and sustainable nanomaterials. Using zebrafish as a model organism for studying the potentially toxic effects of nanomaterials highlights the importance of developing safe and sustainable nanomaterials. Studies conducted on nanomaterials and their toxicity and potential risks to human and environmental health are vital in biomedical sciences. In the present review, we discuss the potential toxicity of nanomaterials (inorganic and organic) and exposure risks based on size, shape, and concentration. The review further explores various types of nanomaterials and their impacts on zebrafish at different levels, indicating that exposure to nanomaterials can lead to developmental defects, changes in gene expressions, and various toxicities. The review also covers the importance of considering natural organic matter and chorion membranes in standardized nanotoxicity testing. While some nanomaterials are biologically compatible, metal and semiconductor nanomaterials that enter the water environment can increase toxicity to aquatic creatures and can potentially accumulate in the human body. Further investigations are necessary to assess the safety of nanomaterials and their impacts on the environment and human health.

Size and charge effects of metal nanoclusters on antibacterial mechanisms.

Nanomaterials, specifically metal nanoclusters (NCs), are gaining attention as a promising class of antibacterial agents. Metal NCs exhibit antibacterial properties due to their ultrasmall size, extensive surface area, and well-controlled surface ligands. The antibacterial mechanisms of metal NCs are influenced by two primary factors: size and surface charge. In this review, we summarize the impacts of size and surface charge of metal NCs on the antibacterial mechanisms, their interactions with bacteria, and the factors that influence their antibacterial effects against both gram-negative and gram-positive bacteria. Additionally, we highlight the mechanisms that occur when NCs are negatively or positively charged, and provide examples of their applications as antibacterial agents. A better understanding of relationships between antibacterial activity and the properties of metal NCs will aid in the design and synthesis of nanomaterials for the development of effective antibacterial agents against bacterial infections. Based on the remarkable achievements in the design of metal NCs, this review also presents conclusions on current challenges and future perspectives of metal NCs for both fundamental investigations and practical antibacterial applications.

Gold-Based Nanostructures for Antibacterial Application.

Bacterial infections have become a fatal threat because of the abuse of antibiotics in the world. Various gold (Au)-based nanostructures have been extensively explored as antibacterial agents to combat bacterial infections based on their remarkable chemical and physical characteristics. Many Au-based nanostructures have been designed and their antibacterial activities and mechanisms have been further examined and demonstrated. In this review, we collected and summarized current developments of antibacterial agents of Au-based nanostructures, including Au nanoparticles (AuNPs), Au nanoclusters (AuNCs), Au nanorods (AuNRs), Au nanobipyramids (AuNBPs), and Au nanostars (AuNSs) according to their shapes, sizes, and surface modifications. The rational designs and antibacterial mechanisms of these Au-based nanostructures are further discussed. With the developments of Au-based nanostructures as novel antibacterial agents, we also provide perspectives, challenges, and opportunities for future practical clinical applications.

Brazilin Isolated from Caesalpina Sappan Wood Induces Intrinsic Apoptosis on A549 Cancer Cell Line by Increasing p53, caspase-9, and caspase-3.

OBJECTIVE: Lung cancer is the leading cause of death among cancer patients. The majority of lung cancer is the Non-Small Lung Carcinoma (NSLC). This study evaluated the potency of brazilin isolated from Caesalpinia sappan wood to induce apoptosis on non-small lung carcinoma cell line, A549, by examining the expression of p53, caspase-9, and caspase-3. METHODS: Brazilin was isolated from Caesalpinia sappan wood following a guided assay and it was determined by using Brazilin®SIGMA as standard. The activity of brazilin on the growth of A549 cell line was analysed by MTT assay and the apoptosis was evaluated by flowcytometer following Annexin V (FITC) and PI staining. The expression of p53, caspase-9, and caspase-3 was examined by immunocytochemistry. RESULT: The IC50 of brazilin on A549 cell line was 43µg/mL. Cell treatment with 20 µg/mL and 40 µg/mL of brazilin significantly increased early apoptosis (p<0.001). Cell treatment with 40 µg/mL  of Brazilin significantly increased late apoptosis (p<0.001). Brazilin significantly increased the expression of p53, Caspase-9, and caspase-3 (p<0.001). CONCLUSION: This study showed evidence of the activity of brazilin to induce intrinsic apoptosis on a NSLC cell line A549.

Antibacterial Pathways in Transition Metal-Based Nanocomposites: A Mechanistic Overview.

Across the planet, outbreaks of bacterial illnesses pose major health risks and raise concerns. Photodynamic, photothermal, and metal ion release effects of transition metal-based nanocomposites (TMNs) were recently shown to be highly effective in reducing bacterial resistance and upsurges in outbreaks. Surface plasmonic resonance, photonics, crystal structures, and optical properties of TMNs have been used to regulate metal ion release, produce oxidative stress, and generate heat for bactericidal applications. The superior properties of TMNs provide a chance to investigate and improve their antimicrobial actions, perhaps leading to therapeutic interventions. In this review, we discuss three alternative antibacterial strategies based on TMNs of photodynamic therapy, photothermal therapy, and metal ion release and their mechanistic actions. The scientific community has made significant efforts to address the safety, effectiveness, toxicity, and biocompatibility of these metallic nanostructures; significant achievements and trends have been highlighted in this review. The combination of therapies together has borne significant results to counter antimicrobial resistance (4-log reduction). These three antimicrobial pathways are separated into subcategories based on recent successes, highlighting potential needs and challenges in medical, environmental, and allied industries.

Copper sulfide with morphology-dependent photodynamic and photothermal antibacterial activities.

Metal chalcogenides have been intensively investigated as antibacterial agents due to their unique structures and superior photoactivities. Herein, various structures of copper sulfide (CuS), a metal chalcogenide, such as microspheres (MSs), nanosheets (NSs), and nanoparticles (NPs), were developed in this work for antibacterial applications. A hydrothermal process was utilized to synthesize CuS MSs, CuS NSs, and CuS NPs. Under simulated solar light and near-infrared (NIR) light irradiation, the antibacterial behaviors, reactive oxygen species (ROS) production, and light-driven antibacterial mechanisms of CuS MSs, CuS NSs, and CuS NPs were demonstrated with the bacterium Escherichia coli (E. coli). Bacterial growth curves and ROS generation tests indicated that CuS NSs and CuS NPs had higher light-driven antibacterial activities than that of CuS MSs. ROS of hydroxyl (·OH) and superoxide anion radicals (O2-) were investigated via an electron spin resonance (ESR) spectroscopic analysis by respectively incubating CuS MSs, CuS NSs, and CuS NPs with E. coli under simulated solar light irradiation. Furthermore, E. coli incubated with CuS NPs and CuS NSs showed substantial bacterial degradation after NIR laser irradiation, which was attributed to their photothermal killing effects. Light-driven antibacterial mechanisms of CuS NSs and CuS NPs were investigated, and we discovered that under simulated solar and NIR light irradiation, CuS NSs and CuS NPs produced photoinduced electrons, and the copper ions and photoinduced electrons then reacted with atmospheric moisture to produce hydroxide and superoxide anion radicals and heat, resulting in bacterial mortality.

Gold Nanorod-Decorated Metallic MoS2 Nanosheets for Synergistic Photothermal and Photodynamic Antibacterial Therapy.

Light-responsive nanocomposites have become increasingly attractive in the biomedical field for antibacterial applications. Visible-light-activated metallic molybdenum disulfide nanosheets (1T-MoS2 NSs) and plasmonic gold nanorods (AuNRs) with absorption at a wavelength of 808 nm were synthesized. AuNR nanocomposites decorated onto 1T-MoS2 NSs (MoS2@AuNRs) were successfully prepared by electrostatic adsorption for phototherapy applications. Based on the photothermal effect, the solution temperature of the MoS2@AuNR nanocomposites increased from 25 to 66.7 °C after 808 nm near-infrared (NIR) laser irradiation for 10 min. For the photodynamic effect, the MoS2@AuNR nanocomposites generated reactive oxygen species (ROS) under visible light irradiation. Photothermal therapy and photodynamic therapy of MoS2@AuNRs were confirmed against E. coli by agar plate counts. Most importantly, the combination of photothermal therapy and photodynamic therapy from the MoS2@AuNR nanocomposites revealed higher antibacterial activity than photothermal or photodynamic therapy alone. The light-activated MoS2@AuNR nanocomposites exhibited a remarkable synergistic effect of photothermal therapy and photodynamic therapy, which provides an alternative approach to fight bacterial infections.

Emerging Trends in Nanomaterials for Antibacterial Applications.

Around the globe, surges of bacterial diseases are causing serious health threats and related concerns. Recently, the metal ion release and photodynamic and photothermal effects of nanomaterials were demonstrated to have substantial efficiency in eliminating resistance and surges of bacteria. Nanomaterials with characteristics such as surface plasmonic resonance, photocatalysis, structural complexities, and optical features have been utilized to control metal ion release, generate reactive oxygen species, and produce heat for antibacterial applications. The superior characteristics of nanomaterials present an opportunity to explore and enhance their antibacterial activities leading to clinical applications. In this review, we comprehensively list three different antibacterial mechanisms of metal ion release, photodynamic therapy, and photothermal therapy based on nanomaterials. These three different antibacterial mechanisms are divided into their respective subgroups in accordance with recent achievements, showcasing prospective challenges and opportunities in clinical, environmental, and related fields.

Facet-dependent gold nanocrystals for effective photothermal killing of bacteria.

Gold-based plasmonic nanocrystals have been extensively developed for noninvasive photothermal therapy. In this study, gold nanorods (AuNRs) with (200) plane and gold nanobipyramids (AuNBPs) with (111) plane were utilized as photothermal agents for noninvasive photothermal therapy. With longitudinal surface plasma bands at ~808 nm, both of AuNRs and AuNBPs revealed photothermal capability and reversibility of laser response under 808-nm near-infrared (NIR) laser irradiation. Moreover, AuNBPs with (111) plane exhibited higher photothermal performance than that of AuNRs with (200) plane under NIR laser irradiation. Density function theory (DFT) simulations revealed that water adsorption energy followed the order Au(111) < Au(100), indicating that the water was easily desorbed on the Au(111) surface for photothermal heating. For the photothermal therapy against Escherichia coli (E. coli), AuNBPs also exhibited higher efficiency compared to that of AuNRs under NIR laser irradiation. Combination of experimental photothermal therapy and DFT simulations demonstrated that AuNBPs with (111) plane were better photothermal agents than that of AuNRs with (100) plane.

High UV-Vis-NIR Light-Induced Antibacterial Activity by Heterostructured TiO2-FeS2 Nanocomposites.

PURPOSE: Antibiotic resistance issues associated with microbial pathogenesis are considered to be one of the most serious current threats to health. Fortunately, TiO2, a photoactive semiconductor, was proven to have antibacterial activity and is being widely utilized. However, its use is limited to the short range of absorption wavelength. METHODS: In this work, heterostructured TiO2-FeS2 nanocomposites (NCs) were successfully prepared by a facile solution approach to enhance light-induced antibacterial activity over a broader absorption range. RESULTS: In TiO2-FeS2 NCs, FeS2 NPs, as light harvesters, can effectively increase light absorption from the visible (Vis) to near-infrared (NIR). Results of light-induced antibacterial activities indicated that TiO2-FeS2 NCs had better antibacterial activity than that of only TiO2 nanoparticles (NPs) or only FeS2 NPs. Reactive oxygen species (ROS) measurements also showed that TiO2-FeS2 NCs produced the highest relative ROS levels. Unlike TiO2 NPs, TiO2-FeS2 NCs, under light irradiation with a 515-nm filter, could absorb light wavelengths longer than 515 nm to generate ROS. In the mechanistic study, we found that TiO2 NPs in TiO2-FeS2 NCs could absorb ultraviolet (UV) light to generate photoinduced electrons and holes for ROS generation, including ⋅O2 - and ⋅OH; FeS2 NPs efficiently harvested Vis to NIR light to generate photoinduced electrons, which then were transferred to TiO2 NPs to facilitate ROS generation. CONCLUSION: TiO2-FeS2 NCs with superior light-induced antibacterial activity could be a promising antibacterial agent against bacterial infections.

One-Pot Synthesis of Thiol-Modified Liquid Crystals Conjugated Fluorescent Gold Nanoclusters.

Gold nanoclusters (AuNCs) and liquid crystals (LCs) have shown great potential in nanobiotechnology applications due to their unique optical and structural properties. Herein, the hardcore of the 4-cyano biphenyl group for commonly used LCs of 4-cyano-4'-pentylbiphenyl (5CB) was utilized to synthesize 4'-(2-mercaptoethyl)-(1,1'-biphenyl)-4-carbonitrile (TAT-12) based on Suzuki coupling and Appel reaction. The structural and optical properties of thiol-modified TAT-12 LCs were demonstrated by nuclear magnetic resonance (NMR) spectroscopy, ultraviolet-visible (UV-vis) spectroscopy and differential scanning calorimetry (DSC). By one-pot synthesis, thiol-modified TAT-12 LCs were used as the ligands to prepare fluorescent gold nanoclusters (AuNCs@TAT-12) according to the Au-S bond between AuNCs and TAT-12. The spectra of UV-vis absorption and X-ray photoelectron spectroscopy (XPS) of AuNCs@TAT-12 indicated that the core of gold of AuNCs@TAT-12 exhibited high gold oxidation states. The fluorescence of AuNCs@TAT-12 was observed with a maximum intensity at ~352 nm coming from TAT-12 on AuNCs@TAT-12 and the fluorescence quantum yield of AuNCs@TAT-12 was calculated to be 10.1%. Furthermore, the fluorescence with a maximum intensity at ~448 nm was attributed to a ligand-metal charge transfer between the ligands of TAT-12 LCs and the core of AuNCs. The image of transmission electron microscopy (TEM) further demonstrated an approximately spherical shape of AuNCs@TAT-12 with an average size of 2.3 nm. A combination of UV-vis absorption spectra, XPS spectra, fluorescence spectra and TEM image, fluorescent AuNCs@TAT-12 were successfully synthesized via one-pot synthesis. Our work provides a practical approach to the synthesis of LCs conjugated AuNCs for future applications in nanobiotechnology.

Nanomaterials for the Photothermal Killing of Bacteria.

An upsurge in the multidrug-resistant (MDR) bacterial pestilence is a global cause for concern in terms of human health. Lately, nanomaterials with photothermal effects have assisted in the efficient killing of MDR bacteria, attributable to their uncommon plasmonic, photocatalytic, and structural properties. Examinations of substantial amounts of photothermally enabled nanomaterials have shown bactericidal effects in an optimized time under near-infrared (NIR) light irradiation. In this review, we have compiled recent advances in photothermally enabled nanomaterials for antibacterial activities and their mechanisms. Photothermally enabled nanomaterials are classified into three groups, including metal-, carbon-, and polymer-based nanomaterials. Based on substantial accomplishments with photothermally enabled nanomaterials, we have inferred current trends and their prospective clinical applications.

Light-Activated Heterostructured Nanomaterials for Antibacterial Applications.

An outbreak of a bacterial contagion is a critical threat for human health worldwide. Recently, light-activated heterostructured nanomaterials (LAHNs) have shown potential as antibacterial agents, owing to their unique structural and optical properties. Many investigations have revealed that heterostructured nanomaterials are potential antibacterial agents under light irradiation. In this review, we summarize recent developments of light-activated antibacterial agents using heterostructured nanomaterials and specifically categorized those agents based on their various light harvesters. The detailed antibacterial mechanisms are also addressed. With the achievements of LAHNs as antibacterial agents, we further discuss the challenges and opportunities for their future clinical applications.

Blockade Effects of Anti-Interferon- (IFN-) γ Autoantibodies on IFN-γ-Regulated Antimicrobial Immunity.

The interferon- (IFN-) γ expression is elicited in response to microbial infections and activates immune surveillance by antimicrobial immune elements to induce microbial killing. Patients with adult-onset immunodeficiency who suffer from recurrent infections with microbes, particularly nontuberculous mycobacteria (NTM), commonly display genetic defects in IFN-γ signaling as well as the generation of anti-IFN-γ autoantibodies (autoAbs). Because IFN-γ is an activator of macrophage differentiation and a proinflammatory activator of innate immunity, the blockade effects of the autoAbs present in NTM patient serum on IFN-γ are hypothesized to regulate the antimicrobial function of macrophages. In the presence of patient serum, IFN-γ-induced type 1 macrophage (M1) differentiation was inhibited in PMA-stimulated human monocytic THP-1 cells. Treatment with patient serum significantly blocked the production of proinflammatory factors, including cytokines/chemokines and reactive oxygen/nitrogen species, by M1 macrophages. Importantly, IFN-γ-facilitated phagocytosis and degradation of heat-killed mycobacterium were decreased by cotreatment with patient serum. These results show the blockade activity of anti-IFN-γ autoAbs on IFN-γ-mediated antimicrobial immunity in macrophages.

Functional neutralization of anti-IFN-γ autoantibody in patients with nontuberculous mycobacteria infection.

Interferon (IFN)-γ is crucial for normal immune surveillance and exhibits immunomodulatory, antimicrobial, and anticancer activity. Patients with nontuberculous mycobacteria (NTM) infection commonly express high levels of anti-IFN-γ autoantibodies (autoAbs) and suffer from recurrent infections due to adult-onset immunodeficiency with defects in IFN-γ immune surveillance. In this study, we developed the methods for determination of anti-IFN-γ autoAbs and then characterized their neutralizing activity in patients with NTM infection. A modified sandwich ELISA-based colorimetric assay followed by immunoblot analysis detected the presence of autoAbs in three out of five serum samples. Serum levels of IFN-γ were decreased. Synthetic peptide binding assay showed variable patterns of epitope recognition in patients positive for anti-IFN-γ autoAbs. Functional tests confirmed that patient serum blocked IFN-γ-activated STAT1 activation and IRF1 transactivation. Furthermore, IFN-γ-regulated inflammation, chemokine production and cytokine production were also blocked. These results provide potentially useful methods to assay anti-IFN-γ autoAbs and to characterize the effects of neutralizing autoAbs on IFN-γ signaling and bioactivity.