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1.
Analyst ; 146(22): 6768-6779, 2021 Nov 08.
Article in English | MEDLINE | ID: mdl-34642716

ABSTRACT

Herein, we propose an array of gold (Au)-coated SU-8 cantilevers with microgrooves for improved maturation of cardiomyocytes and describe its applications to drug-induced cardiac toxicity tests. Firstly, we evaluated the effect of cell culture substrates such as polydimethylsiloxane (PDMS), polyimide (PI), and SU-8 on the cardiomyocyte's maturation. Among these, the SU-8 with microgroove structures exhibits improved cardiomyocyte maturation. Further, thin layers of graphene and Au are coated on SU-8 substrates and the effects of these materials on cardiomyocyte maturation are evaluated by analyzing the expression of proteins such as alpha-actinin, Connexin 43 (Cx43), and Vinculin. While both conductive materials enhanced protein expression when compared to bare SU-8, the Au-coated SU-8 substrates demonstrated superior cardiomyocyte maturation. The cantilever structure is constructed using microgroove patterned SU-8 with and without an Au coating. The Au-coated SU-8 cantilever showed maximum displacement of 17.6 ± 0.3 µm on day 21 compared to bare SU-8 (14.2 ± 0.4 µm) owing to improved cardiomyocytes maturation. Verapamil and quinidine are used to characterize drug-induced changes in the contraction characteristics of cardiomyocytes on bare and Au-coated SU-8 cantilevers. The relative contraction forces and beat rates changed according to the calcium and sodium channel related drugs. Matured cardiomyocytes are less influenced by the drugs compared to immature cardiomyocytes and showed reliable IC50 values. These results indicate that the proposed Au-coated SU-8 cantilever array could help improve the accuracy of toxicity screening results by allowing for the use of cardiomyocytes that have been matured on the drug screening platform.


Subject(s)
Cardiotoxicity , Pharmaceutical Preparations , Gold/toxicity , Humans , Myocardial Contraction , Myocytes, Cardiac
2.
Part Fibre Toxicol ; 18(1): 36, 2021 09 26.
Article in English | MEDLINE | ID: mdl-34565395

ABSTRACT

BACKGROUND: Considering the inevitability for humans to be frequently exposed to nanoparticles (NPs), understanding the biosafety of NPs is important for rational usage. As an important part of the innate immune system, macrophages are widely distributed in vital tissues and are also a dominant cell type that engulfs particles. Mitochondria are one of the most sensitive organelles when macrophages are exposed to NPs. However, previous studies have mainly reported the mitochondrial response upon high-dose NP treatment. Herein, with gold nanoparticles (AuNPs) as a model, we investigated the mitochondrial alterations induced by NPs at a sublethal concentration. RESULTS: At a similar internal exposure dose, different AuNPs showed distinct degrees of effects on mitochondrial alterations, including reduced tubular mitochondria, damaged mitochondria, increased reactive oxygen species, and decreased adenosine triphosphate. Cluster analysis, two-way ANOVA, and multiple linear regression suggested that the surface properties of AuNPs were the dominant determinants of the mitochondrial response. Based on the correlation analysis, the mitochondrial response was increased with the change in zeta potential from negative to positive. The alterations in mitochondrial respiratory chain proteins indicated that complex V was an indicator of the mitochondrial response to low-dose NPs. CONCLUSION: Our current study suggests potential hazards of modified AuNPs on mitochondria even under sublethal dose, indicates the possibility of surface modification in biocompatibility improvement, and provides a new way to better evaluation of nanomaterials biosafety.


Subject(s)
Metal Nanoparticles , Nanoparticles , Gold/toxicity , Humans , Metal Nanoparticles/toxicity , Mitochondria , Nanoparticles/toxicity , Reactive Oxygen Species , Surface Properties
3.
Int J Nanomedicine ; 16: 5017-5036, 2021.
Article in English | MEDLINE | ID: mdl-34326639

ABSTRACT

Introduction: Research on gold nanoparticles (AuNPs) occupies a prominent place in the field of biomedicine nowadays, being their putative toxicity and bioactivity areas of major concern. The green synthesis of metallic nanoparticles using extracts from marine organisms allows the avoidance of hazardous production steps while maintaining features of interest, thus enabling the exploitation of their promising bioactivity. Objective: To synthesize and characterize AuNPs using, for the first time, macroalga Cystoseira tamariscifolia aqueous extract (Au@CT). Methods: Algal aqueous extracts were used for the synthesis of AuNPs, which were characterized using a wide panel of physicochemical techniques and biological assays. Results: The characterization by UV-Vis spectroscopy, transmission electron microscopy, Z-potential and infrared spectroscopy confirmed that Au@CT were stable, spherical and polycrystalline, with a mean diameter of 7.6 ± 2.2 nm. The antioxidant capacity of the extract, prior to and after synthesis, was analyzed in vitro, showing that the high antioxidant potential was not lost during the synthesis. Subsequently, in vitro and in vivo toxicity was screened, by comparing two species of the genus Cystoseira (C. tamariscifolia and C. baccata) and the corresponding biosynthesized gold nanoparticles (Au@CT and Au@CB). Cytotoxicity was tested in mouse (L929) and human (BJ5ta) fibroblast cell lines. In both cases, only the highest (nominal) test concentration of both extracts (31.25 mg/mL) or Au@CB (12.5 mM) significantly affected cell viability, as measured by the MTT assay. These results were corroborated by a Fish Embryo Acute Toxicity (FET) test. Briefly, it was shown that, at the highest (nominal) tested concentration (31.25 mg/mL), CT extract induced significantly higher cytotoxicity and embryotoxicity than CB extract. However, it was demonstrated that Au@CT, but not Au@CB, were generally non-toxic. At sub-lethal (nominal) test concentrations (1.25 and 2.5 mM), Au@CT affected zebrafish embryonic development to a much lesser extent than Au@CB. In vitro wound healing assays also revealed that, while other experimental conditions did not impact cell migration, CT and Au@CT displayed a moderate positive effect. Conclusion: Au@CT and Au@CB display promising features, desirable for biomedical applications, as wound healing.


Subject(s)
Metal Nanoparticles , Seaweed , Animals , Cell Line , Embryonic Development , Gold/toxicity , Green Chemistry Technology , Humans , Metal Nanoparticles/toxicity , Mice , Plant Extracts/toxicity , Zebrafish
4.
ACS Appl Mater Interfaces ; 13(30): 35328-35341, 2021 Aug 04.
Article in English | MEDLINE | ID: mdl-34291912

ABSTRACT

The multifunctional combined nanoplatform has a wide application prospect in the synergistic treatment of cancer. Nevertheless, the traditional treatment of phototherapy is limited by the catalytic nanomaterial itself, so the effect is not satisfactory. Here, the arris of the anisotropic truncated octahedral Au (TOh Au) was coated with noble metal Pt to form a spatial separation structure, which enhanced the local surface plasmonic resonance and thus boosted the photocatalytic effect. In this system, the highly efficient photocatalysis provides a strong guarantee for oncotherapy. On the one hand, the structure of arris deposition adequately improves the efficiency of photothermal conversion, which substantially improves the effectiveness of photothermal therapy. On the other hand, in situ oxygen production of Pt ameliorates tumor hypoxia, and through the O2 self-production and sales mode, the growth and development of tumor were inhibited. Meanwhile, under the enhanced photocatalysis, more O2 were produced, which greatly evolved the treatment effect of photodynamic therapy. In the end, the addition of hyaluronic acid can specifically target osteosarcoma cells while improving the retention time and biocompatibility of the material in the body. Thus, the nanocomposite shows superexcellent synergistic enhancement of photothermal conversion efficiency and photodynamic capability in vitro and in vivo, which provides a potential possibility for osteosarcoma cure.


Subject(s)
Antineoplastic Agents/therapeutic use , Metal Nanoparticles/therapeutic use , Osteosarcoma/drug therapy , Photosensitizing Agents/therapeutic use , Animals , Anisotropy , Antineoplastic Agents/chemistry , Antineoplastic Agents/radiation effects , Antineoplastic Agents/toxicity , Catalysis/radiation effects , Chlorophyllides , Gold/chemistry , Gold/toxicity , Hyaluronic Acid/chemistry , Hyaluronic Acid/toxicity , Infrared Rays , Metal Nanoparticles/chemistry , Metal Nanoparticles/radiation effects , Metal Nanoparticles/toxicity , Mice, Nude , Osteosarcoma/metabolism , Oxygen/metabolism , Photochemotherapy , Photosensitizing Agents/chemistry , Photosensitizing Agents/radiation effects , Photosensitizing Agents/toxicity , Photothermal Therapy , Platinum/chemistry , Platinum/toxicity , Polyethylene Glycols/chemistry , Polyethylene Glycols/toxicity , Porphyrins/chemistry , Porphyrins/radiation effects , Porphyrins/therapeutic use , Reactive Oxygen Species/metabolism , Surface Plasmon Resonance
5.
ACS Appl Mater Interfaces ; 13(30): 35494-35505, 2021 Aug 04.
Article in English | MEDLINE | ID: mdl-34288640

ABSTRACT

Polymer nanocapsules, with a hollow structure, are increasingly finding widespread use as drug delivery carriers; however, quantitatively evaluating the bio-nano interactions of nanocapsules remains challenging. Herein, poly(ethylene glycol) (PEG)-based metal-phenolic network (MPN) nanocapsules of three sizes (50, 100, and 150 nm) are engineered via supramolecular template-assisted assembly and the effect of the nanocapsule size on bio-nano interactions is investigated using in vitro cell experiments, ex vivo whole blood assays, and in vivo rat models. To track the nanocapsules by mass cytometry, a preformed gold nanoparticle (14 nm) is encapsulated into each PEG-MPN nanocapsule. The results reveal that decreasing the size of the PEG-MPN nanocapsules from 150 to 50 nm leads to reduced association (up to 70%) with phagocytic blood cells in human blood and prolongs in vivo systemic exposure in rat models. The findings provide insights into MPN-based nanocapsules and represent a platform for studying bio-nano interactions.


Subject(s)
Blood/metabolism , Metal-Organic Frameworks/chemistry , Nanocapsules/chemistry , Polyethylene Glycols/chemistry , Pyrogallol/analogs & derivatives , Animals , Flow Cytometry/methods , Gold/chemistry , Gold/metabolism , Gold/pharmacokinetics , Gold/toxicity , Humans , Male , Metal Nanoparticles/chemistry , Metal Nanoparticles/toxicity , Metal-Organic Frameworks/metabolism , Metal-Organic Frameworks/pharmacokinetics , Metal-Organic Frameworks/toxicity , Mice , Nanocapsules/toxicity , Particle Size , Polyethylene Glycols/metabolism , Polyethylene Glycols/pharmacokinetics , Polyethylene Glycols/toxicity , Pyrogallol/metabolism , Pyrogallol/pharmacokinetics , Pyrogallol/toxicity , RAW 264.7 Cells , Rats, Sprague-Dawley
6.
ACS Appl Mater Interfaces ; 13(30): 35306-35314, 2021 Aug 04.
Article in English | MEDLINE | ID: mdl-34288648

ABSTRACT

With the long-term and extensive abuse of antibiotics, bacteria can mutate into multidrug-resistant (MDR) strains, resist the existing antibiotics, and escape the danger of being killed. MDR bacteria-caused skin infections are intractable and chronic, becoming one of the most significant and global public-health issues. Thus, the development of novel antimicrobial materials is urgently needed. Non-antibiotic small molecule-modified gold nanoclusters (AuNCs) have great potential as a substitute for commercial antibiotics. Still, their narrow antibacterial spectrum hinders their wide clinical applications. Herein, we report that 4,6-diamino-2-pyrimidinethiol (DAPT)-modified AuNCs (DAPT-AuNCs) can fight against Gram-negative and Gram-positive bacterial strains as well as their MDR counterparts. By modifying DAPT-AuNCs on nanofibrous films, we develop an antibiotic film as innovative dressings for curing incised wounds, which exhibits excellent therapeutic effects on wounds infected by MDR bacteria. Compared to the narrow-spectral one, the broad-spectral antibacterial activity of the DAPT-AuNCs-modified film is more suitable for preventing and treating skin infections caused by various kinds of unknown bacteria. Moreover, the antibacterial films display excellent biocompatibility, implying the great potential for clinical applications.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Bandages , Escherichia coli Infections/drug therapy , Metal Nanoparticles/therapeutic use , Staphylococcal Skin Infections/drug therapy , Animals , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/toxicity , Drug Resistance, Multiple, Bacterial/drug effects , Escherichia coli/drug effects , Escherichia coli Infections/pathology , Female , Gold/chemistry , Gold/toxicity , Human Umbilical Vein Endothelial Cells , Humans , Metal Nanoparticles/chemistry , Metal Nanoparticles/toxicity , Pyrimidines/chemistry , Pyrimidines/toxicity , Rats, Sprague-Dawley , Skin/drug effects , Skin/microbiology , Skin/pathology , Staphylococcal Skin Infections/pathology , Staphylococcus aureus/drug effects , Sulfhydryl Compounds/chemistry , Sulfhydryl Compounds/toxicity , Wound Healing/drug effects
7.
Life Sci ; 284: 119652, 2021 Nov 01.
Article in English | MEDLINE | ID: mdl-34051217

ABSTRACT

AIMS: Gold nanoparticles (AuNPs) have been attracted interests in the various areas of clinical therapeutics. In this study, we investigated the anticancer and antiviral potential activity of AuNPs against influenza A virus and human glioblastoma (GMB) U-87 and U-251 cell lines. MAIN METHODS: Gold nanoparticles (AuNPs) were synthesized by citrate reduction method. Then, ultraviolet-visible spectrophotometry (UV-vis spectra) and electron microscopy analysis confirmed the type, size (mean diameter of 17 nm) and distribution of the particles. The AuNPs in vitro antiviral and anticancer effects was evaluated by hemagglutination inhibition (HAI), tissue culture infectious dose 50 (TCID50), real-time PCR, MTT, flow cytometry, and scratch assays. KEY FINDINGS: The AuNPs were synthesized in spherical with a mean diameter of 17 ± 2 nm and an absorbance peak at 520 nm. The AuNPs were well tolerable by MDCK cells at concentrations up to 0.5µg/ml and they significantly inhibited the hemagglutination and virus infectivity, particularly when added pre- or during virus infection. Furthermore, anticancer results indicated that AuNPs treatment caused the marked induction of apoptosis and reduced growth and migration capability of U-87 and U-251 cell lines in a time-dependent manner. SIGNIFICANCE: The present results suggest that AuNPs provide promising antiviral and anticancer approaches. Further research is needed to fully elucidate the mode of antiviral and anticancer action of AuNPs against influenza virus infection and human glioblastoma cell lines.


Subject(s)
Antineoplastic Agents/pharmacology , Antiviral Agents/pharmacology , Gold/pharmacology , Metal Nanoparticles/chemistry , Animals , Cell Line, Tumor , Cell Migration Assays , Dogs , Glioblastoma/pathology , Gold/toxicity , Humans , Madin Darby Canine Kidney Cells , Metal Nanoparticles/toxicity , Metal Nanoparticles/ultrastructure
8.
Carbohydr Polym ; 266: 118138, 2021 Aug 15.
Article in English | MEDLINE | ID: mdl-34044952

ABSTRACT

Targeting cell surface receptors for specific drug delivery in cancer has garnered lot of attention. Urokinase plasminogen activator receptor (uPAR), a surface biomarker, is overexpressed on many tumours including breast, colorectal, prostate, and ovarian cancers. Binding of growth factor domain (GFD) of urokinase plasminogen activator (uPA) with uPAR lead to its close conformation, and allow somatomedin B domain (SMB) of vitronectin binding by allosteric modulation. In-silico docking of uPAR with GFD and SMB peptides was performed to identify potential binding affinity. Herein, we report fluorescently labeled peptide functionalized AuNPs with a mixed self-assembled monolayer of intercalating chitosan polymer for efficient targeting and imaging of uPAR-positive cells. The biophysical characterization of nanoconjugates and uPAR-specific targeting was assessed by FACS, cell adhesion, and fluorescence imaging. AuNPs/chitosan/GFD+SMB peptides showed higher uptake as compared to AuNPs/chitosan/GFD, and AuNPs/chitosan/SMB that can be utilized as a tool for molecular targeting and imaging in metastasis.


Subject(s)
Chitosan/chemistry , Metal Nanoparticles/chemistry , Neoplasms/diagnostic imaging , Peptides/chemistry , Receptors, Urokinase Plasminogen Activator/metabolism , Cell Line, Tumor , Chitosan/toxicity , Gold/chemistry , Gold/toxicity , Humans , Immobilized Proteins/chemistry , Immobilized Proteins/metabolism , Immobilized Proteins/toxicity , Metal Nanoparticles/toxicity , Microscopy, Fluorescence , Molecular Docking Simulation , Neoplasms/metabolism , Peptides/metabolism , Peptides/toxicity , Protein Binding
9.
ACS Appl Mater Interfaces ; 13(20): 23410-23422, 2021 May 26.
Article in English | MEDLINE | ID: mdl-33978409

ABSTRACT

Nanomedicine is seen as a potential central player in the delivery of personalized medicine. Biocompatibility issues of nanoparticles have largely been resolved over the past decade. Despite their tremendous progress, less than 1% of applied nanosystems can hit their intended target location, such as a solid tumor, and this remains an obstacle to their full ability and potential with a high translational value. Therefore, achieving immune-tolerable, blood-compatible, and biofriendly nanoparticles remains an unmet need. The translational success of nanoformulations from bench to bedside involves a thorough assessment of their design, compatibility beyond cytotoxicity such as immune toxicity, blood compatibility, and immune-mediated destruction/rejection/clearance profile. Here, we report a one-pot process-engineered synthesis of ultrasmall gold nanoparticles (uGNPs) suitable for better body and renal clearance delivery of their payloads. We have obtained uGNP sizes of as low as 3 nm and have engineered the synthesis to allow them to be accurately sized (almost nanometer by nanometer). The synthesized uGNPs are biocompatible and can easily be functionalized to carry drugs, peptides, antibodies, and other therapeutic molecules. We have performed in vitro cell viability assays, immunotoxicity assays, inflammatory cytokine analysis, a complement activation study, and blood coagulation studies with the uGNPs to confirm their safety. These can help to set up a long-term safety-benefit framework of experimentation to reveal whether any designed nanoparticles are immune-tolerable and can be used as payload carriers for next-generation vaccines, chemotherapeutic drugs, and theranostic agents with better body clearance ability and deep tissue penetration.


Subject(s)
Biocompatible Materials , Gold , Immunity, Innate , Metal Nanoparticles , Biocompatible Materials/chemistry , Biocompatible Materials/toxicity , Blood Coagulation/drug effects , Cell Survival/drug effects , Gold/chemistry , Gold/toxicity , Humans , Immunity, Innate/drug effects , Immunity, Innate/physiology , Materials Testing , Metal Nanoparticles/chemistry , Metal Nanoparticles/toxicity , Models, Immunological , Sodium Citrate , THP-1 Cells , Tannins
10.
Folia Histochem Cytobiol ; 59(2): 95-107, 2021.
Article in English | MEDLINE | ID: mdl-33876830

ABSTRACT

INTRODUCTION: Worldwide, nanoparticles especially gold-nanoparticles (Au-NPs) are widely used in medicine, cancer treatment and cosmetic industry. They are easily conjugated with different biomedical and biological agents and effortlessly absorbed with few side effects. The pars distalis of the pituitary gland is considered as the maestro of the endocrine peripheral glands since it secrets trophic hormones that controls their functions. 5-10% of the non-granular pars distalis cells are folliculo-stellate cells (FSCs) that support the granular cells' functions. The aim of the study was to explore the histological and the biochemical effects of repeated exposure to Au-NPs on the pars distalis in adult male albino rats with highlighting the impact on FSCs. MATERIAL AND METHODS: Thirty-six adult male albino rats were divided equally into control group and Au-NPs group (received 40 µg/kg/day of 11 ± 2 nm spherical Au-NPs orally for 2 weeks). Then, rats were euthanized and deposition of Au-NPs in pars distalis was investigated. Biochemical investigations and histological studies including hematoxylin and eosin staining, periodic acid Schiff's reaction, immunohistochemistry (IHC) for S-100, connexin 43 (Cx43) and Cytochrome-C (Cyt-C) as well as electron-microscopic and morphometric studies were carried out. RESULTS: The Au-NPs group demonstrated structural disorganization in the pars distalis, inflammation, congestion and increased extracellular PAS-positive colloid deposition due to the accumulation of Au-NPs. A significant increase in the immunoreactivity of S-100, Cx43 and Cyt-c, along with a significant increase in TNF-a, MDA, and bFGF content in the pituitary homogenates, was noted as compared to the control group. Ultrastructurally, degenerative changes were observed in the secretory cells. FSCs showed proliferation and increased phagocytic activity. CONCLUSIONS: Repetitive exposure of adult male albino rats to Au-NPs prompted the accumulation of these nanoparticles in the pars distalis that was accompanied by cellular degeneration and dysfunction of the secretory cell and proliferation of FSCs. Thus, monitoring of the pars distalis hormonal levels might be useful for early detection of some hazardous effects possibly associated with the use of gold-nanoparticles.


Subject(s)
Metal Nanoparticles/toxicity , Pituitary Gland, Anterior/drug effects , Animals , Apoptosis/drug effects , Cell Proliferation/drug effects , Gold/chemistry , Gold/toxicity , Inflammation/pathology , Inflammation/physiopathology , Male , Metal Nanoparticles/chemistry , Phagocytosis/drug effects , Pituitary Gland, Anterior/pathology , Pituitary Gland, Anterior/ultrastructure , Rats, Wistar
11.
Bioorg Med Chem Lett ; 40: 127929, 2021 05 15.
Article in English | MEDLINE | ID: mdl-33705903

ABSTRACT

A small set of trehalose-centered putative autophagy inducers was rationally designed and synthesized, with the aim to identify more potent and bioavailable autophagy inducers than free trehalose, and to acquire information about their molecular mechanism of action. Several robust, high yield routes to key trehalose intermediates and small molecule prodrugs (2-5), putative probes (6-10) and inorganic nanovectors (12a - thiol-PEG-triazole-trehalose constructs 11) were successfully executed, and compounds were tested for their autophagy-inducing properties. While small molecules 2-11 showed no pro-autophagic behavior at sub-millimolar concentrations, trehalose-bearing PEG-AuNPs 12a caused measurable autophagy induction at an estimated 40 µM trehalose concentration without any significant toxicity at the same concentration.


Subject(s)
Autophagy/drug effects , Neuroprotective Agents/pharmacology , Trehalose/analogs & derivatives , Trehalose/pharmacology , Drug Design , Gold/chemistry , Gold/toxicity , HeLa Cells , Humans , Metal Nanoparticles/chemistry , Metal Nanoparticles/toxicity , Neuroprotective Agents/chemical synthesis , Neuroprotective Agents/toxicity , Polyethylene Glycols/chemistry , Polyethylene Glycols/toxicity , Trehalose/toxicity
12.
Pak J Biol Sci ; 24(2): 261-267, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33683056

ABSTRACT

BACKGROUND AND OBJECTIVE: Nanotechnology is a cumbersome field used in industrial, medical and environmental applications. Abundant information regarding the genotoxicity of gold nanoparticles is available, but limited information is available about the genotoxicity of enzymes and bioconjugates of gold nanoparticles from microbial sources. The present investigation reveals the genotoxicity of bioconjugate of tyrosinase and gold nanoparticles from Streptomyces sp. MATERIALS AND METHODS: Tyrosinase and gold nanoparticles were isolated from Streptomyces tuirus DBZ39 and employed for the development of bioconjugates by the flocculation assay method. Methyl thiazole (MTT) assay, transmission electron microscopy, Dynamic Light Scattering (DLS) and UV-vis absorption spectroscopy were used for the investigation. RESULTS: Bioconjugate showed a significant genotoxic effect at a concentration of 18 µL and at least 10 µL. Bioconjugate of tyrosinase and gold nanoparticles by Streptomyces tuirus DBZ39 revealed a more expressed genotoxic effect than nanoparticles alone. The efficacy of gold nanoparticles was expected to improve the bonding of tyrosine due to their catalytic properties. CONCLUSION: This innovative concept of the application of Tyr-AuNps bioconjugate can be used for the development of powerful weapons in medicinal fields. The introduction of bioconjugates of enzymes and nanoparticles in the field of drug design and cancer imaging will be a fundamental breakthrough in medicine.


Subject(s)
Bone Marrow/drug effects , DNA Damage , Gold/toxicity , Lymphocytes/drug effects , Metal Nanoparticles/toxicity , Monophenol Monooxygenase/toxicity , Mutagenicity Tests , Streptomyces/enzymology , Animals , Bone Marrow/pathology , Cells, Cultured , Gold/metabolism , Humans , Lymphocytes/pathology , Mice , Monophenol Monooxygenase/genetics , Monophenol Monooxygenase/metabolism , Nanotechnology , Streptomyces/genetics
13.
J Environ Sci Health A Tox Hazard Subst Environ Eng ; 56(4): 413-433, 2021.
Article in English | MEDLINE | ID: mdl-33593243

ABSTRACT

The initial cyanide (CN-) concentration and amount of co-contaminants in GCTs can inhibit bacterial growth and reduce the CN--degrading ability of bacteria. Several microorganisms can biotransform a wide range of organic and inorganic industrial contaminants into nontoxic compounds. However, active enzymatic CN- metabolism processes are mostly constrained by the physical and chemical characteristics of GCTs. High concentrations of toxic metal co-contaminants, such as, Pb, and Cr, and factors, such as pH, temperature, and oxygen concentration create oxidative stress and limit the CN--degrading potential of cyanotrophic strains. The effects of such external and internal factors on the CN--degrading ability of bacteria hinder the selection of suitable microorganisms for CN- biodegradation. Therefore, understanding the effects of the physicochemical properties of GCTs on cyanobacteria strains can help identify suitable microbes and favorable environmental conditions to promote microbial growth and can also help design efficient CN- biodegradation processes. In this review, we present a detailed analysis of the physicochemical properties of GCTs and their effects on microbial CN- degradation.


Subject(s)
Cyanides/toxicity , Cyanobacteria/drug effects , Environmental Pollutants/toxicity , Gold/toxicity , Biodegradation, Environmental/drug effects , Cyanides/chemistry , Cyanides/metabolism , Cyanobacteria/growth & development , Cyanobacteria/metabolism , Environmental Pollutants/chemistry , Environmental Pollutants/metabolism , Gold/chemistry , Gold/metabolism , Industrial Waste/analysis
14.
Acta Chim Slov ; 67(1): 304-311, 2020 Mar.
Article in English | MEDLINE | ID: mdl-33558935

ABSTRACT

A hybrid scaffold containing gold nanorods and lysozyme amyloid fibrils has been fabricated, and the effect of surface modification on improving nanostructure assembly on the biological template has been investigated. The nanohybrid system was characterized by monitoring surface plasmon resonance bands, dynamic light scattering spectroscopy, Thioflavin-T assay, and transmission electron microscopy. Surface of gold nanorods (GNRs) was modified with polystyrene sulfonate (PSS), and possible difference in assembly of the pristine and modified nanostructures was compared upon interaction with amyloid fibrils. Analysis of transmission electron microscopy showed that changing the surface charge of GNRs with biocompatible polymer improved electrostatic interactions between the nanostructures and amyloid fibril templates. Analysis of cell viability assays also showed that surface functionalization of GNRs remarkably improved biocompatibility of the nanoscaffold. Results of this study encourage utilization of modification strategies to fabricate a new generation of nanoscaffolds with fruitful applications in regenerative medicine.


Subject(s)
Amyloidogenic Proteins/chemistry , Muramidase/chemistry , Nanotubes/chemistry , Amyloidogenic Proteins/toxicity , Animals , Cell Survival/drug effects , Chickens , Gold/chemistry , Gold/toxicity , Hep G2 Cells , Humans , Muramidase/toxicity , Nanotubes/toxicity
15.
Part Fibre Toxicol ; 18(1): 5, 2021 01 21.
Article in English | MEDLINE | ID: mdl-33478543

ABSTRACT

BACKGROUND: Inhalation exposure to nanomaterials in workplaces can include a mixture of multiple nanoparticles. Such ambient nanoparticles can be of high dissolution or low dissolution in vivo and we wished to determine whether co-exposure to particles with different dissolution rates affects their biokinetics. METHODS AND RESULTS: Rats were exposed to biosoluble silver nanoparticles (AgNPs, 10.86 nm) and to biopersistent gold nanoparticles (AuNPs, 10.82 nm) for 28 days (6-h/day, 5-days/week for 4 weeks) either with separate NP inhalation exposures or with combined co-exposure. The separate NPs mass concentrations estimated by the differential mobility analyzer system (DMAS) were determined to be 17.68 ± 1.69 µg/m3 for AuNP and 10.12 ± 0.71 µg/m3 for AgNP. In addition, mass concentrations analyzed by atomic absorption spectrometer (AAS) via filter sampling were for AuNP 19.34 ± 2.55 µg/m3 and AgNP 17.38 ± 1.88 µg/m3 for separate exposure and AuNP 8.20 ± 1.05 µg/m3 and AgNP 8.99 ± 1.77 µg/m3 for co-exposure. Lung retention and clearance were determined on day 1 (6-h) of exposure (E-1) and on post-exposure days 1, 7, and 28 (PEO-1, PEO-7, and PEO-28, respectively). While the AgNP and AuNP deposition rates were determined to be similar due to the similarity of NP size of both aerosols, the retention half-times and clearance rates differed due to the difference in dissolution rates. Thus, when comparing the lung burdens following separate exposures, the AgNP retention was 10 times less than the AuNP retention at 6-h (E-1), and 69, 89, and 121 times lower less than the AuNP retention at PEO-1, PEO-7, and PEO-28, respectively. In the case of AuNP+AgNP co-exposure, the retained AgNP lung burden was 14 times less than the retained AuNP lung burden at E-1, and 26, 43, and 55 times less than the retained AuNP lung burden at PEO-1, PEO-7, and PEO-28, respectively. The retention of AuNP was not affected by the presence of AgNP, but AgNP retention was influenced in the presence of AuNP starting at 24 h after the first day of post day of exposure. The clearance of AgNPs of the separate exposure showed 2 phases; fast (T1/2 3.1 days) and slow (T1/2 48.5 days), while the clearance of AuNPs only showed one phase (T1/2 .81.5 days). For the co-exposure of AuNPs+AgNPs, the clearance of AgNPs also showed 2 phases; fast (T1/2 2.2 days) and slow (T1/2 28.4 days), while the clearance of AuNPs consistently showed one phase (T1/2 54.2 days). The percentage of Ag lung burden in the fast and slow clearing lung compartment was different between separate and combined exposure. For the combined exposure, the slow and fast compartments were each 50% of the lung burden. For the single exposure, 1/3 of the lung burden was cleared by the fast rate and 2/3 of the lung burden by the slow rate. CONCLUSIONS: The clearance of AgNPs follows a two- phase model of fast and slow dissolution rates while the clearance of AuNPs could be described by a one- phase model with a longer half-time. The co-exposure of AuNPs+AgNPs showed that the clearance of AgNPs was altered by the presence of AuNPs perhaps due to some interaction between AgNP and AuNP affecting dissolution and/or mechanical clearance of AgNP in vivo.


Subject(s)
Metal Nanoparticles , Particulate Matter/toxicity , Animals , Gold/toxicity , Inhalation Exposure/analysis , Lung , Metal Nanoparticles/toxicity , Particle Size , Rats , Silver/toxicity
16.
Biomarkers ; 26(3): 240-247, 2021 May.
Article in English | MEDLINE | ID: mdl-33459570

ABSTRACT

CONTEXT: The Au-TiO2NPs have a wide range of applications and can easily enter the cells. Due to their properties, they can cause toxicity. OBJECTIVE: It was aimed to test the toxic effects of Au-TiO2 NPs in the brain, heart, kidney and liver of rats in this work. MATERIALS AND METHODS: All used rats in this work were treated using diverse concentrations (doses) of NPs (100 and 200 mg/kg bw) for 21 days. SOD, CAT, AChE activities and MDA, H2O2, NO contents were evaluated in different organs. RESULTS: The Au-TiO2 NPs exposure induced biochemical changes in different organs of rats in view of oxidative stress and neurotoxicity by the alteration of the activity of the enzyme of neurotransmitter (AChE activity). CONCLUSION: The Au-TiO2 NPs have the potential to interact with rat's biochemical status and cause undesirable effects. One of those damaging effects was oxidative stress and neurotoxicity. CLINICAL SIGNIFICANCE: The study signifies the impact of usage of Au-TiO2 NPs in the medical field for further exploration.


Subject(s)
Brain/drug effects , Gold/toxicity , Metal Nanoparticles/toxicity , Neurotoxicity Syndromes/etiology , Oxidative Stress/drug effects , Titanium/toxicity , Animals , Biomarkers/metabolism , Brain/metabolism , Kidney/drug effects , Kidney/metabolism , Kidney/pathology , Liver/drug effects , Liver/metabolism , Liver/pathology , Male , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/pathology , Neurotoxicity Syndromes/metabolism , Neurotoxicity Syndromes/pathology , Rats, Wistar , Time Factors
17.
Cells ; 10(1)2021 01 07.
Article in English | MEDLINE | ID: mdl-33430453

ABSTRACT

Gold nanoparticles (AuNPs) have demonstrated outstanding performance in many biomedical applications. Their safety is recognised; however, their effects on the immune system remain ill defined. Antigen-presenting cells (APCs) are immune cells specialised in sensing external stimulus and in capturing exogenous materials then delivering signals for the immune responses. We used primary macrophages (Ms) and dendritic cells (DCs) of mice as an APC model. Whereas AuNPs did not alter significantly Ms and DCs functions, the exposure to AuNPs affected differently Ms and DCs in their responses to subsequent stimulations. The secretion of inflammatory molecules like cytokines (IL-6, TNF-α), chemokine (MCP-1), and reactive oxygen species (ROS) were altered differently in Ms and DCs. Furthermore, the metabolic activity of Ms was affected with the increase of mitochondrial respiration and glycolysis, while only a minor effect was seen on DCs. Antigen presentation to T cells increased when DCs were exposed to AuNPs leading to stronger Th1, Th2, and Th17 responses. In conclusion, our data provide new insights into the complexity of the effects of AuNPs on the immune system. Although AuNPs may be considered as devoid of significant effect, they may induce discrete modifications on some functions that can differ among the immune cells.


Subject(s)
Dendritic Cells/metabolism , Gold/pharmacology , Macrophages/metabolism , Metal Nanoparticles/chemistry , Animals , Antigen-Presenting Cells/cytology , Antigen-Presenting Cells/drug effects , Antigen-Presenting Cells/metabolism , Biomarkers/metabolism , Cell Line , Cell Membrane/drug effects , Cell Membrane/metabolism , Cell Survival/drug effects , Dendritic Cells/drug effects , Epitopes/drug effects , Glycolysis/drug effects , Gold/toxicity , Macrophages/drug effects , Metal Nanoparticles/toxicity , Mice, Inbred C57BL , Mitochondria/drug effects , Mitochondria/metabolism , Phagocytosis/drug effects , Signal Transduction/drug effects , T-Lymphocytes/drug effects , T-Lymphocytes/metabolism
18.
Ecotoxicol Environ Saf ; 210: 111775, 2021 Mar 01.
Article in English | MEDLINE | ID: mdl-33421722

ABSTRACT

The aim of the present study was the assessment of the sub-chronic effects of silver (AgNPs) and gold nanoparticles (AuNPs) of 40 nm primary size either stabilised with citrate (CIT) or coated with polyethylene glycol (PEG) on the freshwater invertebrate Gammarus fossarum. Silver nitrate (AgNO3) was used as a positive control in order to study the contribution of silver ions potentially released from AgNPs on the observed effects. A multibiomarker approach was used to assess the long-term effects of AgNPs and AuNPs 40 nm on molecular, cellular, physiological and behavioural responses of G. fossarum. Specimen of G. fossarum were exposed for 15 days to 0.5 and 5 µgL-1 of CIT and PEG AgNPs and AuNPs 40 nm in the presence of food. A significant uptake of both Ag and Au was observed in exposed animals but was under the toxic threshold leading to mortality of G. fossarum. Silver nanoparticles (CIT-AgNPs and PEG-AgNPs 40 nm) led to an up-regulation of Na+K+ATPase gene expression. An up-regulation of Catalse and Chitinase gene expressions due to exposure to PEG-AgNPs 40 nm was also observed. Gold nanoparticles (CIT and PEG-AuNPs 40 nm) led to an increase of CuZnSOD gene expression. Furthermore, both AgNPs and AuNPs led to a more developed digestive lysosomal system indicating a general stress response in G. fossarum. Both AgNPs and AuNPs 40 nm significantly affected locomotor activity of G. fossarum while no effects were observed on haemolymphatic ions and ventilation.


Subject(s)
Gold/toxicity , Metal Nanoparticles/toxicity , Silver/toxicity , Amphipoda/drug effects , Animals , Citric Acid/toxicity , Digestive System/drug effects , Locomotion/drug effects , Male , Polyethylene Glycols/toxicity
19.
J Toxicol Sci ; 45(12): 795-800, 2020.
Article in English | MEDLINE | ID: mdl-33268679

ABSTRACT

We have previously reported the cytotoxicity and various biological responses of organic-inorganic hybrid molecules. However, because all the molecules used were electrophilic, the effect of the hybrid molecule without electrophilicity remains unclear. The glutathione-protected gold nanocluster, Au25(SG)18, is an organic-inorganic hybrid molecule that shows a low intramolecular polarity and high stability. In this study, we examined the cytotoxicity and intracellular accumulation of Au25(SG)18 in cultured vascular endothelial cells and compared these characteristics with those of negatively charged gold nanoparticles (AuNPs). Both Au25(SG)18 and AuNPs accumulated in vascular endothelial cells in a dose-dependent manner without cytotoxicity and more accumulation was observed at low cell densities. However, Au25(SG)18 accumulated significantly less than AuNPs in the cells. These results suggest that the intramolecular polarity of organic-inorganic hybrid molecules could regulate intracellular accumulation.


Subject(s)
Endothelial Cells/metabolism , Endothelium, Vascular/cytology , Gold/metabolism , Gold/toxicity , Metal Nanoparticles , Animals , Cattle , Cell Count , Cells, Cultured , Cytotoxins , Dose-Response Relationship, Drug , Drug Stability , Glutathione , Particle Size
20.
J Biomed Nanotechnol ; 16(6): 985-996, 2020 Jun 01.
Article in English | MEDLINE | ID: mdl-33187593

ABSTRACT

Cetuximab-conjugated gold nanoparticles are known to target cancer cells, but display toxicity towards normal kidney, liver and endothelial cells in vitro. In this study, we investigated their pharmacokinetics, biodistribution and toxicity after intravenous administration in healthy mice. Our data showed that these nanoparticles were rapidly cleared from the blood and accumulated mainly in the liver and spleen with long-term retention. Acute liver injury, inflammatory activity and vascular damage were transient and negligible, as confirmed by the liver functionality tests and serum marker analysis. There was no sign of altered liver, kidney, lung and spleen morphology up to 4 weeks post-injection. After 6 months, kidney casts and splenic apoptosis appeared to be more prevalent than in the controls. Furthermore, occasional immune cell infiltration was observed in the lungs. Therefore, we recommend additional in vivo studies, in order to investigate the long-term toxicity and elimination of gold nanoparticles after multiple dosing in their preclinical validation as new targeted anti-cancer therapies.


Subject(s)
Metal Nanoparticles , Nanoparticles , Animals , Endothelial Cells , Gold/metabolism , Gold/toxicity , Metal Nanoparticles/toxicity , Mice , Spleen/metabolism , Tissue Distribution
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